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1. Impact of systemic therapies in metastatic melanoma of unknown primary: A study from MELBASE, a French multicentric prospective cohort

Author: Rousset, Perrine, Dalle, Stéphane, Mortier, Laurent, Dereure, Olivier, Dalac, Sophie, Dutriaux, Caroline, Leccia, Marie-Thérèse, Legoupil, Delphine, Brunet-Possenti, Florence, de Quatrebarbes, Julie, Grob, Jean-Jacques, Saiag, Philippe, Maubec, Eve, Stoebner, Pierre-Emmanuel, Granel-Brocard, Florence, Arnault, Jean-Philippe, Allayous, Clara, Oriano, Bastien, Lebbé, Celeste, Montaudié, Henri, Centre Hospitalier Universitaire de Nice (CHU Nice), Centre Léon Bérard [Lyon], Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Thérapies Laser Assistées par l'Image pour l'Oncologie - U 1189 (ONCO-THAI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Pathogenesis and Control of Chronic and Emerging Infections (PCCEI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)-Etablissement français du don du sang [Montpellier]-Université de Montpellier (UM), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de Dermatologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Bordeaux [Bordeaux], Centre Hospitalier Universitaire [Grenoble] (CHU), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois], Service de dermatologie, vénéreologie et cancérologie cutanée [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Hôpital Ambroise Paré [AP-HP], Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), Biomarqueurs et essais cliniques en Cancérologie et Onco-Hématologie (BECCOH), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay, Hôpital Avicenne [AP-HP], Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), 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), Service de Dermatologie et Allergologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), CHU Amiens-Picardie, Service de Dermatologie [AP-HP Hôpital Saint-Louis], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hôpital Hôtel-Dieu [Paris], Service de Dermatologie [Nice], Hôpital Archet 2 [Nice] (CHU), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (1965 - 2019) (UNS), and 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)-Université Côte d'Azur (UCA)
Subjects: MESH: Humans, Survival, Systemic therapy, MESH: Melanoma, MESH: Immunotherapy, MESH: Skin Neoplasms, Dermatology, Melanoma of unknown primary, Advanced melanoma, Targeted therapy, MESH: Neoplasms, Unknown Primary, MESH: Skin, MESH: Progression-Free Survival, Adverse events, Melanoma of known primary, Chemotherapy, Immunotherapy, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology
Abstract: International audience; Background: Clinical outcomes of advanced melanoma of unknown primary (MUP) in the era of novel therapies have been scarcely studied.Objective: To investigate the efficacy and safety of systemic treatments in patients with advanced MUP compared to patients with stage-matched melanoma of known cutaneous primary (cMKP).Methods: Based on the nationwide MelBase prospective database, this study included advanced melanoma patients treated from March 2013 to June 2021 with first-line immunotherapies, targeted therapies, or chemotherapy. Co-primary outcomes were progression-free survival and overall survival. Secondary outcome was treatment-related toxicities. Multivariate and propensity score analyses were performed.Results: Of 1882 patients, 265 (14.1%) had advanced MUP. Patients with advanced MUP displayed more often unfavorable initial prognostic factors than those with cMKP. Progression-free and overall survival did not differ significantly between the groups (P = .73 and P = .93, respectively), as well as treatment-related toxicity rate and severity, regardless of treatment type.Limitations: No record of standard diagnostic criteria of MUP used in the participating centers.Conclusions: Although patients with MUP had less favorable baseline prognostic factors, they benefited from the novel therapies as much as those with cMKP. They should be managed according to similar strategies.
Published: 2023

2. Risk of irAEs in patients with autoimmune diseases treated by immune checkpoint inhibitors for stage III or IV melanoma: results from a matched case-control study

Author: Léo Plaçais, Stéphane Dalle, Olivier Dereure, Sabiha Trabelsi, Sophie Dalac, Delphine Legoupil, Henri Montaudié, Jean-Philippe Arnault, Julie De Quatrebarbes, Philippe Saiag, Florence Brunet-Possenti, Thierry Lesimple, Eve Maubec, François Aubin, Florence Granel-Brocard, Jean-Jacques Grob, Pierre-Emmanuel Stoebner, Clara Allayous, Bastien Oriano, Caroline Dutriaux, Laurent Mortier, Céleste Lebbe, AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Immunologie des maladies virales, auto-immunes, hématologiques et bactériennes (IMVA-HB), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris-Saclay, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre Léon Bérard [Lyon], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Pathogenesis and Control of Chronic and Emerging Infections (PCCEI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université des Antilles (UA)-Etablissement français du don du sang [Montpellier]-Université de Montpellier (UM), Centre Hospitalier Universitaire [Grenoble] (CHU), Service de Dermatologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Laboratoire de Neurosciences de Brest (LNB), Université de Brest (UBO), Service de Dermatologie [Nice], Hôpital Archet 2 [Nice] (CHU), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (1965 - 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)-Université Côte d'Azur (UCA), CHU Amiens-Picardie, Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois], Hôpital Ambroise Paré [AP-HP], Université de Versailles Saint-Quentin-en-Yvelines (UVSQ), AP-HP - Hôpital Bichat - Claude Bernard [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CRLCC Eugène Marquis (CRLCC), Hôpital Avicenne [AP-HP], Université Paris 13 (UP13), Service de Dermatologie et Allergologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de dermatologie, vénéreologie et cancérologie cutanée [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), 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), Service de Dermatologie [AP-HP Hôpital Saint-Louis], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Hôpital Hôtel-Dieu [Paris], CHU Bordeaux [Bordeaux], and Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille)
Subjects: MESH: Humans, MESH: Immune Checkpoint Inhibitors, MESH: Melanoma, Immunology, Autoimmunity, MESH: Retrospective Studies, Therapeutics, MESH: Antineoplastic Agents, Immunological, MESH: Case-Control Studies, General Biochemistry, Genetics and Molecular Biology, MESH: Prospective Studies, Autoimmune Diseases, Antineoplastic Agents, Immunological, Rheumatology, [SDV.MHEP.RSOA]Life Sciences [q-bio]/Human health and pathology/Rhumatology and musculoskeletal system, Immune System Diseases, MESH: Autoimmune Diseases, MESH: Immune System Diseases, Case-Control Studies, Immunology and Allergy, Humans, Prospective Studies, Immune Checkpoint Inhibitors, Melanoma, Retrospective Studies
Abstract: ObjectiveTo quantify the risk of immune-related adverse events (irAEs) in patients with pre-existing autoimmune disease (pAID) treated by immune checkpoint inhibitors (ICIs) for stage III or IV melanoma.MethodsCase–control study performed on a French multicentric prospective cohort of patients with melanoma, matched for irAE risk factors and oncological staging. Risk of irAE was assessed by logistic regression.Results110 patients with pAID were included and matched with 330 controls, from March 2013 to October 2020. Over a median follow-up period of 7.2 months for cases and 6.9 months for controls, the ORs of developing all-grade and grade ≥3 irAEs among cases compared with controls were 1.91 (95% CI (1.56 to 2.27)) and 1.44 (95% CI (1.08 to 1.82)), respectively. Patients with pAID had an increased risk of multiple irAEs (OR 1.46, 95% CI (1.15 to 2.67)) and a shorter time to irAE onset. In contrast, there were no difference in irAE-related mortality nor in the rate of treatment discontinuation, and a landmark analysis revealed a better survival at 24 months among cases (p=0.02). Thirty per cent of cases experienced a pAID flare during follow-up, and baseline immunosuppression did not prevent irAE occurrence. Last, we report associations between the pAID clinical subsets and organ-specific irAEs.ConclusionIn our study, patients with pAID were at greater risk of all-grade, severe and multiple irAEs, yet had a better 24-month survival than controls. Thus, patients with pAID should be eligible for ICI therapy but benefit from a close monitoring for irAE occurrence, especially during the first months of therapy.
Published: 2022

3. Transient abdominal telangiectasia of the newborn

Author: Antoine Finon, Emmanuelle Bourrat, C. Labreze, Maryam Piram, Cécile Juzot, Marine Fournet, Thomas Hubiche, Sébastien Barbarot, Didier Bessis, Christine Chiaverini, Vannina Seta, Annabel Maruani, Hélène Aubert, Cyril Flamant, Olivia Boccara, Ludovic Martin, Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Imagine - Institut des maladies génétiques (IHU) (Imagine - U1163), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Universitaire de Nice (CHU Nice), CIC Plurithématique de Nantes, Institut National de la Santé et de la Recherche Médicale (INSERM)-Ministère des Affaires sociales et de la Santé-Direction générale de l'offre de soins (DGOS)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Dermatologie [Nice], Hôpital Archet 2 [Nice] (CHU), Service de dermatologie [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], MethodS in Patients-centered outcomes and HEalth ResEarch (SPHERE), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), and Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques
Subjects: Skin manifestations, medicine.medical_specialty, Pediatrics, medicine.diagnostic_test, business.industry, [SDV]Life Sciences [q-bio], Butterfly wing, Physical examination, Dermatology, Poor weight gain, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, 030225 pediatrics, Pediatrics, Perinatology and Child Health, medicine, Neonatology, medicine.symptom, Telangiectasia, business, ComputingMilieux_MISCELLANEOUS
Abstract: We report 20 newborns who developed, at a median age of 7 days, large abdominal patches of radially arranged purplish telangiectasia in a bilateral and symmetrical pattern in relation to the midline, creating a "butterfly wing" pattern. Clinical examination was normal in 13 newborns, six newborns had abdominal distention, and one newborn had poor weight gain due to inadequate breastfeeding. Most lesions spontaneously resolved within 3 months and did not reoccur for 19 newborns. Transient abdominal telangiectasia of the newborn (TATN) appears to be a distinctive entity that has not been previously described.
Published: 2021

4. ITGBL1 is a new immunomodulator that favors development of melanoma tumors by inhibiting natural killer cells cytotoxicity

Author: Corine Bertolotto, Thomas Strub, Henri Montaudié, Pierre Close, Thierry Passeron, Karine Bille, Arnaud Jacquel, Najla El Hachem, Robert Ballotti, Maeva Gesson, Meri K. Tulic, Guillaume E. Beranger, Alexandra Picard-Gauci, Yann Cheli, Nicolas Nottet, Centre méditerranéen de médecine moléculaire (C3M), 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 National de la Santé et de la Recherche Médicale (INSERM), Université de Liège, Service de Dermatologie [Nice], Hôpital Archet 2 [Nice] (CHU), Université Nice Sophia Antipolis (1965 - 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)-Université Côte d'Azur (UCA), and BERTOLOTTO-BALLOTTI, BERTOLOTTO-BALLOTTI
Subjects: 0301 basic medicine, Cytotoxicity, Immunologic, Cancer Research, Carcinogenesis, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, lcsh:RC254-282, 03 medical and health sciences, 0302 clinical medicine, Immune system, [SDV.CAN] Life Sciences [q-bio]/Cancer, Melanocyte differentiation, Downregulation and upregulation, Cell Line, Tumor, medicine, Animals, Immunologic Factors, Cytotoxicity, Letter to the Editor, Melanoma, ITGBL1, Cell Proliferation, Microphthalmia-Associated Transcription Factor, MITF, Integrin beta1, Correction, lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens, Microphthalmia-associated transcription factor, medicine.disease, Immune checkpoint, 3. Good health, RUNX2, Killer Cells, Natural, Mice, Inbred C57BL, 030104 developmental biology, Oncology, 030220 oncology & carcinogenesis, Cancer research, Molecular Medicine
Abstract: Erratum inCorrection to: ITGBL1 is a new immunomodulator that favors development of melanoma tumors by inhibiting natural killer cells cytotoxicity.Cheli Y, Tulic MK, El Hachem N, Nottet N, Jacquel A, Gesson M, Strub T, Bille K, Picard-Gauci A, Montaudié H, Beranger GE, Passeron T, Close P, Bertolotto C, Ballotti R.Mol Cancer. 2021 Jan 27;20(1):21. doi: 10.1186/s12943-021-01319-5.PMID: 33504341 Free PMC article. No abstract available.; International audience; Resistances to immunotherapies remains a major hurdle towards a cure for melanoma in numerous patients. An increase in the mesenchymal phenotype and a loss of differentiation have been clearly associated with resistance to targeted therapies. Similar phenotypes have been more recently also linked to resistance to immune checkpoint therapies. We demonstrated here that the loss of MIcrophthalmia associated Transcription Factor (MITF), a pivotal player in melanocyte differentiation, favors the escape of melanoma cells from the immune system. We identified Integrin beta-like protein 1 (ITGBL1), a secreted protein, upregulated in anti-PD1 resistant patients and in MITFlow melanoma cells, as the key immunomodulator. ITGBL1 inhibited immune cell cytotoxicity against melanoma cells by inhibiting NK cells cytotoxicity and counteracting beneficial effects of anti-PD1 treatment, both in vitro and in vivo. Mechanistically, MITF inhibited RUNX2, an activator of ITGBL1 transcription. Interestingly, VitaminD3, an inhibitor of RUNX2, improved melanoma cells to death by immune cells. In conclusion, our data suggest that inhibition of ITGBL1 might improve melanoma response to immunotherapies.
Published: 2021

5. Google trends peut-il prédire de nouveaux signes cutanés durant les épidémies ?

Author: S. Huynh, Khaled Ezzedine, Tu Anh Duong, Guillaume Lamé, Thomas Hubiche, Service de dermatologie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Laboratoire Génie Industriel (LGI), CentraleSupélec-Université Paris-Saclay, Service de Dermatologie [Nice], and Hôpital Archet 2 [Nice] (CHU)
Subjects: [SPI.OTHER]Engineering Sciences [physics]/Other, [SHS.GESTION]Humanities and Social Sciences/Business administration, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Dermatology, [INFO.INFO-RO]Computer Science [cs]/Operations Research [cs.RO], [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology, ComputingMilieux_MISCELLANEOUS, 3. Good health
Abstract: Introduction Google trends (GT) permet de connaitre la frequence a laquelle un terme a ete cherche dans Google. Son interet a ete demontre pour predire et detecter des foyers epidemiques. Cependant, aucune etude n’a evalue son interet pour detecter de nouveaux signes cutanes en integrant l’influence de facteurs externes i.e. confinement et couverture mediatique des nouveaux signes. L’objectif de ce travail est d’evaluer l’activite et l’influence de facteurs externes sur les recherches des signes cutanes lies a SARS-Cov-2 dans plusieurs pays. Materiel et methodes Deux recherches sur GT en incluant les termes 1/« orteil(s) » et « engelure(s) », et 2/« Coronavirus » ont ete realisees pour la periode 1er janvier - 16 mai 2020 dans 6 pays (France, Etats-Unis, Grande Bretagne (GB), Espagne, Italie et Allemagne). Pour chacun des pays, les facteurs externes i.e. date de confinement et annonce grand media des signes cutanes ont ete collectes. La sequence de recherche signes cutanes versus coronavirus a ete visualisee sur une figure commune en utilisant le ratio signes cutanes/coronavirus. Une regression lineaire par segments, en integrant les dates de confinement et d’annonce mediatique de chaque pays a ete realisee pour etudier l’impact des facteurs externes sur les recherches. Resultats Les volumes relatifs de recherche ou relative search volumes (RSVs) fournis par GT et lies aux engelures sont croissants sur la periode debutant mi-mars jusqu’aux annonces mediatiques (ou elle atteint un pic dans 3 pays). Le ratio RSVs engelures/RSVs Coronavirus, montre que l’interet relatif pour les engelures croit dans l’ensemble des pays. La regression lineaire par segments met en evidence : – apres le debut du confinement, un effet de seuil negatif (p – post annonces mediatiques, un effet de seuil positif et une pente decroissante (p – aucune variation en Allemagne. Le coefficient de determination R2 ajuste entre 0,305 et 0,351 pour la France, Espagne, Italie, et Etats-Unis montre une correlation moyenne entre le RSV et le temps. Discussion L’augmentation des RSVs signes cutanes avant les medias des la mi-mars temoigne d’un signal precoce present sur Google. Dans 4 pays, cet interet culmine au moment des annonces. Le ratio engelure/coronavirus montre cependant un seuil eleve de recherches apres les annonces en comparaison avec le coronavirus seul. Conclusion Un systeme d’alerte sur Google permettrait une detection precoce de symptomes cutanes associes a une maladie emergente. La prise en compte de facteurs, influencant les requetes, est necessaire pour garantir la fiabilite de tels systemes d’alerte.
Published: 2020

6. The Influence of Media Coverage and Governmental Policies on Google Queries Related to COVID-19 Cutaneous Symptoms: Infodemiology Study

Author: Guillaume Lamé, Thomas Hubiche, Tu Anh Duong, Solene Huynh Dagher, Khaled Ezzedine, Guillaume, Lamé, Service de dermatologie [Mondor], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Laboratoire Génie Industriel (LGI), CentraleSupélec-Université Paris-Saclay, Service de Dermatologie [Nice], Hôpital Archet 2 [Nice] (CHU), Epidemiology in Dermatology and Evaluation in Therapeutics (EpiDermE), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), Chaire Avenir Santé Numérique [Créteil] (CASN), Institut Mondor de Recherche Biomédicale (IMRB), and Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)-Institut National de la Santé et de la Recherche Médicale (INSERM)-IFR10-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12)
Subjects: medicine.medical_specialty, 020205 medical informatics, MEDLINE, Google Trends, skin lesions, Health Informatics, Media coverage, Public Policy, 02 engineering and technology, online health information, Skin Diseases, infodemiology, chilblains, Infodemiology, lesion, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Public health surveillance, Pandemic, Epidemiology, 0202 electrical engineering, electronic engineering, information engineering, medicine, Humans, Public Health Surveillance, Mass Media, Chilblains, Internet, Original Paper, media coverage, media, Public Health, Environmental and Occupational Health, Outbreak, COVID-19, medicine.disease, United States, 3. Good health, Europe, Search Engine, dermatology, Geography, trend, [SDV.SPEE] Life Sciences [q-bio]/Santé publique et épidémiologie, [SDV.SPEE]Life Sciences [q-bio]/Santé publique et épidémiologie, Demography
Abstract: Background During COVID-19, studies have reported the appearance of internet searches for disease symptoms before their validation by the World Health Organization. This suggested that monitoring of these searches with tools including Google Trends may help monitor the pandemic itself. In Europe and North America, dermatologists reported an unexpected outbreak of cutaneous acral lesions (eg, chilblain-like lesions) in April 2020. However, external factors such as public communications may also hinder the use of Google Trends as an infodemiology tool. Objective The study aimed to assess the impact of media announcements and lockdown enforcement on internet searches related to cutaneous acral lesions during the COVID-19 outbreak in 2020. Methods Two searches on Google Trends, including daily relative search volumes for (1) “toe” or “chilblains” and (2) “coronavirus,” were performed from January 1 to May 16, 2020, with the United States, the United Kingdom, France, Italy, Spain, and Germany as the countries of choice. The ratio of interest over time in “chilblains” and “coronavirus” was plotted. To assess the impact of lockdown enforcement and media coverage on these internet searches, we performed an interrupted time-series analysis for each country. Results The ratio of interest over time in “chilblains” to “coronavirus” showed a constant upward trend. In France, Italy, and the United Kingdom, lockdown enforcement was associated with a significant slope change for “chilblain” searches with a variation coefficient of 1.06 (SE 0.42) (P=0.01), 1.04 (SE 0.28) (P Conclusions To date, the association between chilblain-like lesions and COVID-19 remains controversial; however, our results indicate that Google queries of “chilblain” were highly influenced by media coverage and government policies, indicating that caution should be exercised when using Google Trends as a monitoring tool for emerging diseases.
Published: 2020

7. Clinical and haemodynamic risk factors associated with discrepancies in lower limb length with capillary malformations: data from the national paediatric French cohort CONAPE

Author: Ali Dadban, Groupe de Recherche de la Société Française de Dermatologie Pédiatrique, C. Eschard, Christine Chiaverini, Nathalie Beneton, Sophie Leducq, Gérard Lorette, Olivia Boccara, Mahtab Samimi, Xavier Balguerie, Juliette Mazereeuw-Hautier, Patrice Plantin, Ludovic Martin, Pierre Vabres, Baptiste Morel, Sébastien Barbarot, Catherine Droitcourt, M Durieux-Verde, Agnès Caille, Didier Bessis, Annabel Maruani, Service de dermatologie (CHRU de Tours), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Université Francois Rabelais [Tours], Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de dermatologie (CHU de Toulouse), CHU Toulouse [Toulouse], Centre de référence national des Maladies Génétiques à Expression Cutanée (MAGEC), Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département de dermatologie, CHU Angers, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Service de Dermatologie [Nice], Hôpital Archet 2 [Nice] (CHU), Service de dermatologie (CHU de Reims), Centre Hospitalier Universitaire de Reims (CHU Reims), Service de dermatologie [CH Le Mans], Centre Hospitalier Le Mans (CH Le Mans), Service de Dermatologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de Dermatologie [Rouen], Hôpital Charles Nicolle [Rouen]-CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Service de dermatologie et vénérologie [Hôpital Laënnec, site de Quimper], CH Cornouaille, Département de dermatologie [CHU de Montpellier], Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Service de dermatologie [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de dermatologie [CHU d'Amiens-Picardie], CHU Amiens-Picardie, Service de Dermatologie [Rennes] = Dermatology [Rennes], CHU Pontchaillou [Rennes], Service de radiographie pédiatrique (CHRU Tours), French Ministry of Social Affairs and Health (French National Program of Clinical Research [PHRC], 2009, Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM), CHU Necker - Enfants Malades [AP-HP], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris]
Subjects: Male, capillary malformations, medicine.medical_specialty, Duplex ultrasonography, Vascular Malformations, Radiography, Hemodynamics, Dermatology, 030204 cardiovascular system & hematology, Cohort Studies, lymphatic, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Risk Factors, port-wine-stains, medicine, Humans, Prospective Studies, Child, Prospective cohort study, overgrowth, geographic, venous, Leg, Ultrasonography, Doppler, Duplex, business.industry, medicine.disease, Parkes Weber syndrome, Capillaries, Leg Length Inequality, 3. Good health, Surgery, Child, Preschool, Overgrowth syndrome, Cohort, Female, Nuclear medicine, business, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology, Blood Flow Velocity, Cohort study
Abstract: SummaryBackground Genetics discoveries have allowed for better understanding capillary malformations (CMs) with overgrowth syndrome. However, molecular analyses are still not easy to perform or interpret. Other analytical methods are needed. Objective We aimed to identify clinical and hemodynamic factors associated with leg length discrepancy (LLD) in children with CM of lower limbs. Methods Data were obtained from the multicentre French national cohort CONAPE (COhorte Nationale d'enfants atteints d'Angiome Plan de membrE inferieur), including children from 2 to 12 years old with CM of lower limbs. Clinical characteristics were prospectively collected. Hemodynamic factors were measured by an echographer who calculated the arterial blood flow (ABF) in both lower limbs. An ABF difference ≥50% between the two lower limbs was considered relevant. LLD ≥ 2% was determined by the same radiologist on centralized radiographs. Results We analyzed data at baseline for 96 children. The mean (SD) age was 5.6 (3.1) years; 49 (51%) were male; and 14 (15%) showed LLD. Thirty-two patients (33%) had venous anomalies, 13 (14%) lymphatic anomalies, and in 1 child, diagnosis of Parkes Weber syndrome was made. Only increased circumference above the knee was more frequent with than without LLD (50% vs 13%, p=0.02). In all, 10/79 patients (13%) showed a difference in ABF ≥50%: 4 had LLD. The frequency of differences in ABF ≥50% was greater with than without LLD [33.3% (n=4/12) vs 9.0% (n=6/67), p=0.04]. Conclusions ABF measured by Duplex ultrasonography is a simple, low-cost and non-invasive complementary examination for help in detecting LLD, with a difference ≥ 50% possibly associated. This article is protected by copyright. All rights reserved.
Published: 2018

8. Effectiveness and safety of dupilumab for the treatment of atopic dermatitis in a real-life French multicenter adult cohort

Author: A. Schoeffler, Ziad Reguiai, Audrey Lasek, Anne-Sophie Dillies, Jonathan Giovannelli, Nadia Raison-Peyron, Marie-Christine Ferrier le Bouedec, Aurélie Du Thanh, Sarah Faiz, Anne Dompmartin, Laurent Misery, Marie-Aleth Richard, J. Delaunay, Jean-Philippe Lacour, Sandrine Rappelle-Duruy, Jean-Philippe Arnault, Céline Podevin, Anne-Bénédicte Duval-Modeste, Jean-David Bouaziz, Angèle Soria, Amélie Walter-Lepage, Julien Sénéchal, Delphine Staumont-Sallé, François Aubin, Catherine Droitcourt, N. Bellon, Sébastien Barbarot, Stéphane Barete, Florence Tetart, Marie Jachiet, Emmanuel Mahé, Nathalie Beneton, Edouard Begon, Audrey Nosbaum, A. Valois, C. Morice, Service de Dermatologie, Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Lille Inflammation Research International Center - U 995 (LIRIC), Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de Dermatologie [AP-HP Hôpital Saint-Louis], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Polyclinique Courlancy (PC), Polyclinique de Courlancy, Immunologie de l'allergie cutanée et vaccination – Immunology of skin allergy and vaccination, Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Saint Vincent de Paul de Lille, Groupement des Hôpitaux de l'Institut Catholique de Lille (GHICL), Université catholique de Lille (UCL)-Université catholique de Lille (UCL), Université de Clermont-Ferrand, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de dermatologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Université de Rouen Normandie (UNIROUEN), Normandie Université (NU), Service de Dermatologie [Rouen], Hôpital Charles Nicolle [Rouen], Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Service de dermatologie, Hôpital Augustin Morvan-Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Département de dermatologie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Hôpital Saint-Jacques-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service de Dermatologie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de Dermatologie [Rennes] = Dermatology [Rennes], CHU Pontchaillou [Rennes], CHU Tenon [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université (SU), Centre d'Immunologie et des Maladies Infectieuses (CIMI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Sorbonne Université (SU)-Centre National de la Recherche Scientifique (CNRS), Service de dermatologie [CHU d'Amiens-Picardie], CHU Amiens-Picardie, Département de dermatologie, CHU Angers, Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Service de Dermatologie et pathologies vasculaires [CH Argenteuil], Centre Hospitalier Victor Dupouy, Centre d'études et de recherche sur les services de santé et la qualité de vie (CEReSS), Aix Marseille Université (AMU), Centre hospitalier régional Metz-Thionville (CHR Metz-Thionville), Service de Dermatologie [Nice], Hôpital Archet 2 [Nice] (CHU), Centre Hospitalier René Dubos [Pontoise], CHU La Milétrie, Université de Picardie Jules Verne (UPJV), Service de Dermatologie, Hôpital Joseph Imbert, Centre Hospitalier d'Arles, CHU Pitié-Salpêtrière [AP-HP], Service de dermatologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Le Mans (CH Le Mans), Hôpital d'Instruction des Armées Sainte Anne, Service de Santé des Armées, Neurofibromatosis Clinic, Centre hospitalier universitaire de Nantes (CHU Nantes), Biothérapies des maladies génétiques et cancers, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), CCSD, Accord Elsevier, Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS), Groupe Hospitalier de l'Institut Catholique de Lille (GHICL), Normandie Université (NU)-Normandie Université (NU)-Hôpital Charles Nicolle [Rouen], Centre Hospitalier Régional Universitaire de Brest (CHRU Brest)-Hôpital Augustin Morvan, Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Hôpital Saint-Jacques-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Sorbonne Université (SU)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre d'Immunologie et de Maladies Infectieuses (CIMI), Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), and Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Adult, Male, medicine.medical_specialty, Injections, Subcutaneous, [SDV]Life Sciences [q-bio], Kaplan-Meier Estimate, Dermatology, Antibodies, Monoclonal, Humanized, Risk Assessment, Severity of Illness Index, Eczema Area and Severity Index, Drug Administration Schedule, Dermatitis, Atopic, Cohort Studies, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Interquartile range, Internal medicine, dupilumab, medicine, conjunctivitis, Humans, SCORAD, Adverse effect, Proportional Hazards Models, Retrospective Studies, Dose-Response Relationship, Drug, medicine.diagnostic_test, business.industry, Antibodies, Monoclonal, Atopic dermatitis, Dermatology Life Quality Index, medicine.disease, adultsatopic dermatitis, Dupilumab, 3. Good health, [SDV] Life Sciences [q-bio], 030220 oncology & carcinogenesis, Cohort, biotherapy, Female, France, Patient Safety, business, eosinophilia
Abstract: International audience; BackgroundDupilumab is the first biologic available to treat atopic dermatitis (AD). Its effectiveness and safety were demonstrated in clinical trials.ObjectiveWe sought to assess the effectiveness and safety of dupilumab in adults with AD in a real-life French multicenter retrospective cohort.MethodsWe included patients treated during March 2017-April 2018. Efficacy outcomes, including Scoring Atopic Dermatitis (SCORAD) and Eczema Area and Severity Index (EASI) scores, were collected at baseline and 3 months when available. Adverse events (AEs) were recorded at follow-up.ResultsWe included 241 patients. The median ± interquartile range (IQR) follow-up time was 3.8 ± 3.7 months. A ≥75% improvement in SCORAD was achieved in 27 of 163 (16.6%) patients, and a ≥75% improvement in EASI was achieved in 40 of 82 (48.8%) patients. The median SCORAD and EASI scores at 3 months were significantly lower than those at baseline (SCORAD ± IQR, 25 ± 21 vs 56 ± 27.4, P < 10−9 and EASI ± IQR, 4.1 ± 6.8 vs 17.9 ± 15.4, P < 10−9, respectively). Conjunctivitis was reported in 84 of 241 (38.2%) patients. The proportion with eosinophilia (>500 cells/mm3) during follow-up (57%) was higher than that at baseline (33.7%) (n = 172, P < 10−6). Dupilumab was stopped in 42 cases; 27 patients stopped because of AEs.LimitationsNo control group, missing data.ConclusionThis real-life study demonstrated a similar dupilumab effectiveness as that seen in clinical trials, but it also revealed a higher frequency of conjunctivitis and eosinophilia.
Published: 2019

9. Association of Time From Primary Diagnosis to First Distant Relapse of Metastatic Melanoma With Progression of Disease and Survival

Author: Céleste Lebbé, Anais Vallet, Raphaël Porcher, D. Legoupil, Thierry Lesimple, Bernard Guillot, Philippe Saiag, Jean-Philippe Lacour, Eve Maubec, Caroline Dutriaux, Florence Brunet-Possenti, Marie-Thérèse Leccia, Brigitte Dréno, Julie De Quatrebarbes, Bastien Oriano, Florence Granel-Brocard, Jean-Philippe Arnault, for MelBase, Laurent Mortier, Pierre-Emmanuel Stoebner, Clara Allayous, Stéphane Dalle, Sophie Dalac, François Aubin, Service de Dermatologie [AP-HP Hôpital Saint-Louis], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre de Diagnostic et de Thérapeutique, Hôpital de l’Hôtel-Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), CHU Bordeaux [Bordeaux], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), 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), Hôpital du Bocage, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Biomarqueurs et essais cliniques en Cancérologie et Onco-Hématologie (BECCOH), Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Université Paris-Saclay, Institut National du Cancer [Boulogne Billancourt] (INC), Service de Dermatologie [Nice], Hôpital Archet 2 [Nice] (CHU), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Département d'oncologie médicale [Rennes], CRLCC Eugène Marquis (CRLCC), Service de dermatologie [CHU d'Amiens-Picardie], CHU Amiens-Picardie, Département de dermatologie, Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC)-Hôpital Saint-Jacques-Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service de Dermatologie et Allergologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Service de dermatologie [Avicenne], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Avicenne [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Sorbonne Paris Nord, Centre de Recherche en Cancérologie Nantes-Angers (CRCNA), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM)-Hôtel-Dieu de Nantes-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Laennec-Centre National de la Recherche Scientifique (CNRS)-Faculté de Médecine d'Angers-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de dermatologie [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Laboratoire Dynamique des Protéines et Modélisation (LDPM), Université des Antilles et de la Guyane (UAG), Centre de Recherche Épidémiologie et Statistique Sorbonne Paris Cité (CRESS (U1153 / UMR_A_1125 / UMR_S_1153)), Université Paris Diderot - Paris 7 (UPD7)-Université Sorbonne Paris Cité (USPC)-Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National de la Recherche Agronomique (INRA), Hôpital Hôtel-Dieu [Paris], Immunologie, dermatologie, oncologie, Oncodermatologie, immunologie et cellules souches cutanées (IDO (U976 / UMR_S 976)), and Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, Oncology, medicine.medical_specialty, Skin Neoplasms, Time Factors, [SDV.CAN]Life Sciences [q-bio]/Cancer, Dermatology, Cohort Studies, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Interquartile range, Internal medicine, medicine, Humans, Prospective Studies, Progression-free survival, Neoplasm Metastasis, Stage (cooking), Prospective cohort study, Melanoma, Aged, Original Investigation, business.industry, Hazard ratio, MESH: Cohort studies, Melanoma/diagnosis, Middle aged, Skin neoplasms/diagnosis, Survival rate, Progression-Free survival, Middle Aged, Prognosis, Chemotherapy regimen, Progression-Free Survival, 3. Good health, Survival Rate, 030220 oncology & carcinogenesis, Localized disease, Cohort, Disease Progression, Female, France, Neoplasm Recurrence, Local, business, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology
Abstract: International audience; The prognosis of advanced melanoma has been greatly improved by new therapeutic agents and clinicians rely on dynamic signals to drive their therapeutic choices. Although the kinetics of metastatic disease seem to be correlated with survival, progression of the localized disease is not predictable.Objective: To assess whether progression of metastatic disease is associated with the time to the first distant recurrence of melanoma.Design, Setting, and Participants: This study was conducted from March 1, 2013, to September 1, 2017, among 638 adults with unresectable stage III or IV melanoma within the French multicentric prospective cohort MelBase. Patients treated with first-line immunotherapies, targeted therapies, or chemotherapy were included. Patients with unknown primary or de novo metastatic melanoma were not included. Data were analyzed from March 1, 2013, to December 1, 2017.Main Outcomes and Measures: The date of primary excision and time to first distant recurrence, progression-free survival, and overall survival were collected. Cox proportional hazards regression models were planned to assess the association between time to first distant recurrence and progression-free survival or overall survival, which was evaluated in terms of hazard ratio (HR). Time to recurrence was analyzed both as a continuous and categorical variable (24 months).Results: A total of 638 patients (272 women and 366 men; median age, 64 years [interquartile range, 52-73 years]) were included in the study. The median time from primary excision to first distant recurrence was 25 months (interquartile range, 12-55 months). There was no evidence of association of the time to recurrence with progression-free survival, both when analyzed as a continuous variable (HR, 0.99; 95% CI, 0.99-1.01) or after categorization (12-24 months: HR, 0.75; 95% CI, 0.56-1.02; >24 months: HR, 0.62; 95% CI; 0.47-1.01). There was no evidence of association of the time to recurrence with overall survival, both when analyzed as a continuous variable (HR, 0.99; 95% CI, 0.98-1.02) or after categorization (12-24 months: HR, 0.76; 95% CI, 0.54-1.07; >24 months: HR, 0.61; 95% CI, 0.54-1.03). Those results remained nonsignificant after stratification by treatment.Conclusions and Relevance: In the MelBase cohort, time to recurrence of metastatic melanoma appears not to be associated with progression-free survival or overall survival.
Published: 2019

10. Impact of radiotherapy administered simultaneously with systemic treatment in patients with melanoma brain metastases within MelBase, a French multicentric prospective cohort

Author: Stéphane Dalle, Raphaël Porcher, Thierry Lesimple, Marie-Thérèse Leccia, Jean-Philippe Lacour, Sophie Dalac, D. Legoupil, Pauline Tétu, Sameh Mohamed, A. Ballon, Florence Brunet-Possenti, Céleste Lebbé, Clara Allayous, Laurent Mortier, François Aubin, Julie De Quatrebarbes, Pierre-Emmanuel Stoebner, Caroline Dutriaux, Bastien Oriano, Brigitte Dréno, Bernard Guillot, Philippe Saiag, Marie Beylot-Barry, Immunologie humaine, physiopathologie & immunothérapie (HIPI (UMR_S_976 / U976)), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Paris (UP), Centre de Diagnostic et de Thérapeutique, Hôpital de l’Hôtel-Dieu [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Laboratoire de Cytogénétique Constitutionnelle [Hospices civils de Lyon], Hospices Civils de Lyon (HCL), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Centre Hospitalier Universitaire [Grenoble] (CHU), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de Dermatologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Bordeaux [Bordeaux], Service de Dermatologie [Nice], Hôpital Archet 2 [Nice] (CHU), Hôpital Ambroise Paré [AP-HP], AP-HP - Hôpital Bichat - Claude Bernard [Paris], Centre Hospitalier Annecy-Genevois [Saint-Julien-en-Genevois], Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Hôpital Morvan - CHRU de Brest (CHU - BREST ), Centre Eugène Marquis (CRLCC), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Centre hospitalier universitaire de Nantes (CHU Nantes), Service de biostatistique et information médicale de l’hôpital Saint Louis (Equipe ECSTRA) (SBIM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut national du cancer [Boulogne] (INCA)-Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université de Paris (UP), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Paris Cité (UPCité), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Cité (UPCité), and CCSD, Accord Elsevier
Subjects: Male, 0301 basic medicine, Oncology, Cancer Research, medicine.medical_specialty, genetic structures, Propensity score, medicine.medical_treatment, [SDV.CAN]Life Sciences [q-bio]/Cancer, Systemic therapy, Targeted therapy, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, medicine, Humans, Prospective Studies, cardiovascular diseases, Stage (cooking), Prospective cohort study, Melanoma, Aged, Proportional Hazards Models, Radiotherapy, Brain Neoplasms, business.industry, MESH: Brain Neoplasms/radiotherapy, Melanoma/drug therapy, Melanoma/radiotherapy, Middle Aged, Brain metastases, medicine.disease, equipment and supplies, Advanced melanoma, Combined Modality Therapy, Confidence interval, 3. Good health, Radiation therapy, 030104 developmental biology, 030220 oncology & carcinogenesis, Propensity score matching, cardiovascular system, Female, Immunotherapy, business, circulatory and respiratory physiology
Abstract: International audience; Background: Melanoma brain metastases (MBMs) are historically associated with poor prognosis. Radiation therapy is conventionally associated with a high local control rate. Development of targeted therapy and immunotherapy has improved overall survival (OS) and intracranial response rate, but about 50% of patients failed to respond to these novel therapies. The objective of this study was to assess the impact of combined radiotherapy (cRT) on overall survival in a large multicenter real-life prospective cohort of patients with MBM treated with immunotherapy or targeted therapy.Patients and methods: Clinical data from 262 patients with MBM were collected via MelBase, a French multicentric biobank prospectively enrolling unresectable stage III or IV melanoma. Two groups were defined: patients receiving cRT (cRT group) or not receiving cRT (no-cRT group). Primary end-point was OS. Propensity score weighting was used to correct for indication bias.Results: Among the 262 patients, 93 (35%) received cRT (cRT group). The patients were treated with immunotherapy in 69% and 60% and with targeted therapy in 31% and 40% of the cRT and no-cRT groups, respectively. With a median follow-up of 6.9 months, median OS was 16.8 months and 6.9 months in the cRT and no-cRT groups, respectively. After propensity score weighting, cRT was associated with longer OS (hazard ratio = 0.6, 95% confidence interval: 0.4-0.8; p=0.007). Median OS after ponderation was 15.3 months and 6.2 months in the cRT and no-cRT groups, respectively.Conclusion: This study shows that cRT may be associated with a significant decrease of 40% in the risk of death in patients with MBM treated with systemic therapy.
Published: 2019

11. Dermatological manifestations in cardiofaciocutaneous syndrome: a prospective multicentric study of 45 mutation‐positive patients

Author: N. Pouvreau, F. Giuliano, Smail Hadj-Rabia, M.‐L. Jacquemont, Emmanuelle Bourrat, Juliette Mazereeuw-Hautier, Yline Capri, Didier Lacombe, F. Morice‐picard, Christine Chiaverini, Cédric Baumann, Didier Bessis, J. Miquel, Pierre Sarda, M. Best, Nicole Philip, Yoann Vial, C. Abadie, Alain Verloes, Safa Aouinti, Lucile Pinson, C. Pernet, Sabine Sigaudy, Stéphanie Mallet, David Geneviève, Christine Coubes, Anne-Claire Bursztejn, Nicolas Molinari, Hélène Cavé, Béatrice Parfait, Stanislas Lyonnet, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Pathogénèse et contrôle des infections chroniques (PCCI), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), CHU de Bordeaux Pellegrin [Bordeaux], Hôpital Robert Debré Paris, Hôpital Robert Debré, CHU Pontchaillou [Rennes], Hôpital de la Colombière, Université de Montpellier (UM), Département de génétique [Robert Debré], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de Dermatologie [Nice], Hôpital Archet 2 [Nice] (CHU), Hôpital Arnaud de Villeneuve [CHRU Montpellier], Dpt génétique médicale [CHU Nice], Centre Hospitalier Universitaire de Nice (CHU Nice), CHU Necker - Enfants Malades [AP-HP], CHU Sud Saint Pierre [Ile de la Réunion], Hôpital de la Timone [CHU - APHM] (TIMONE), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Rennes (UR), Institut Montpelliérain Alexander Grothendieck (IMAG), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), AP-HP - Hôpital Cochin Broca Hôtel Dieu [Paris], Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Michel-Avella, Amandine, Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), CHU Toulouse [Toulouse], Université de Rennes (UNIV-RENNES), and Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)
Subjects: Heart Defects, Congenital, Male, Proto-Oncogene Proteins B-raf, medicine.medical_specialty, Adolescent, MAP Kinase Kinase 2, MAP Kinase Kinase 1, Administration, Oral, Dermatology, Cardiofaciocutaneous syndrome, Administration, Cutaneous, Keratosis Pilaris, Acitretin, Diagnosis, Differential, 030207 dermatology & venereal diseases, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Costello syndrome, Ectodermal Dysplasia, Medicine, Humans, Prospective Studies, Young adult, Prospective cohort study, Child, Genetic Association Studies, Sirolimus, Palmoplantar hyperkeratosis, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, Costello Syndrome, Noonan Syndrome, Facies, medicine.disease, 3. Good health, Failure to Thrive, Treatment Outcome, Child, Preschool, Mutation, Noonan syndrome, Female, France, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug
Abstract: BACKGROUND: Data on dermatological manifestations of cardiofaciocutaneous syndrome (CFCS) remain heterogeneous and almost without expert dermatological classification. OBJECTIVES: To describe the dermatological manifestations of CFCS; to compare them with the literature findings; to assess those discriminating CFCS from other RASopathies, including Noonan syndrome (NS) and Costello syndrome (CS); and to test for dermatological phenotype-genotype correlations. METHODS: We performed a 4-year, large, prospective, multicentric, collaborative dermatological and genetic study. RESULTS: Forty-five patients were enrolled. Hair abnormalities were ubiquitous, including scarcity or absence of eyebrows and wavy or curly hair in 73% and 69% of patients, respectively. Keratosis pilaris (KP), ulerythema ophryogenes (UO), palmoplantar hyperkeratosis (PPHK) and multiple melanocytic naevi (MMN; over 50 naevi) were noted in 82%, 44%, 27% and 29% of patients, respectively. Scarcity or absence of eyebrows, association of UO and PPHK, diffuse KP and MMN best differentiated CFCS from NS and CS. Oral acitretin may be highly beneficial for therapeutic management of PPHK, whereas treatment of UO by topical sirolimus 1% failed. No significant dermatological phenotype-genotype correlation was determined. CONCLUSIONS: A thorough knowledge of CFCS skin manifestations would help in making a positive diagnosis and differentiating CFCS from CS and NS.
Published: 2019

12. Dermatological manifestations in Noonan syndrome: a prospective multicentric study of 129 patients positive for mutation

Author: Hélène Cavé, Nicole Philip, Christine Chiaverini, M.‐L. Jacquemont, Emmanuelle Bourrat, Valérie Pallure, J. Miquel, Juliette Mazereeuw-Hautier, Clarisse Baumann, Yline Capri, Stéphanie Mallet, Sophie Guillaumont, Federico Manna, Claire Jeandel, Smail Hadj-Rabia, Yoann Vial, C. Pernet, Pierre Sarda, M. Willems, Lucile Pinson, C. Abadie, Sabine Sigaudy, Christine Coubes, F. Giuliano, Didier Lacombe, Fanny Morice-Picard, P. Blanchet, Didier Bessis, David Geneviève, M. Best, Alain Verloes, A.-C. Bursztejn, Nicolas Molinari, Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), AP-HP Hôpital universitaire Robert-Debré [Paris], Service de Dermatologie [Nice], Hôpital Archet 2 [Nice] (CHU), Service de génétique médicale, Université de Bordeaux (UB)-CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Laboratoire de Physique Théorique et Astroparticules (LPTA), Université Montpellier 2 - Sciences et Techniques (UM2)-Institut National de Physique Nucléaire et de Physique des Particules du CNRS (IN2P3)-Centre National de la Recherche Scientifique (CNRS), Met Office Hadley Centre, Joint Centre for Hydrometeorological Research, Wallingford, United Kingdom, ONERA - The French Aerospace Lab [Châtillon], ONERA, Service de Dermatologie et Allergologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Département de génétique [Robert Debré], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-AP-HP Hôpital universitaire Robert-Debré [Paris], Service de génétique médicale [Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Arnaud de Villeneuve, Dpt génétique médicale [CHU Nice], Centre Hospitalier Universitaire de Nice (CHU Nice), Saint-Pierre Institute, Service de dermatologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Laboratoire d'études en Géophysique et océanographie spatiales (LEGOS), Institut de Recherche pour le Développement (IRD)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Centre National d'Études Spatiales [Toulouse] (CNES)-Observatoire Midi-Pyrénées (OMP), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Production du lait (PL), AGROCAMPUS OUEST-Institut National de la Recherche Agronomique (INRA), Service de dermatologie (CHU de Toulouse), CHU Toulouse [Toulouse], Centre Hospitalier Saint Jean de Perpignan, Centre de résonance magnétique biologique et médicale (CRMBM), Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)-Centre National de la Recherche Scientifique (CNRS), Interactions et dynamique des environnements de surface (IDES), Université Paris-Sud - Paris 11 (UP11)-Institut national des sciences de l'Univers (INSU - CNRS)-Centre National de la Recherche Scientifique (CNRS), Génétique et épigénétique des maladies métaboliques, neurosensorielles et du développement (Inserm U781), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Département de génétique médicale, maladies rares et médecine personnalisée [CHRU de Montpellier], Unité fonctionnelle de génétique clinique, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7), Génétique des maladies multifactorielles (GMM), Université de Lille, Droit et Santé-Centre National de la Recherche Scientifique (CNRS), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Joint Centre for Hydro-Meteorological Research, Met Office Hadley Centre (JCHMR), United Kingdom Met Office [Exeter], ONERA-Université Paris Saclay (COmUE), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Institut national des sciences de l'Univers (INSU - CNRS)-Observatoire Midi-Pyrénées (OMP), Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Météo France-Centre National d'Études Spatiales [Toulouse] (CNES)-Centre National de la Recherche Scientifique (CNRS)-Institut de Recherche pour le Développement (IRD)-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-AGROCAMPUS OUEST, Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro)-Institut national d'enseignement supérieur pour l'agriculture, l'alimentation et l'environnement (Institut Agro), Département de génétique médicale, maladies rares et médecine personnalisée [CHRU Montpellier], Cellules Souches, Plasticité Cellulaire, Médecine Régénératrice et Immunothérapies (IRMB), Université de Montpellier (UM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Université Paris Diderot - Paris 7 (UPD7)-Hôpital Robert Debré-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Physiologie & médecine expérimentale du Cœur et des Muscles [U 1046] (PhyMedExp), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Hôpital de la Timone [CHU - APHM] (TIMONE), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Robert Debré-Université Paris Diderot - Paris 7 (UPD7)
Subjects: musculoskeletal diseases, Neuroblastoma RAS viral oncogene homolog, Adult, Male, congenital, hereditary, and neonatal diseases and abnormalities, medicine.medical_specialty, Adolescent, [SDV]Life Sciences [q-bio], DNA Mutational Analysis, Protein Tyrosine Phosphatase, Non-Receptor Type 11, Dermatology, medicine.disease_cause, Keratosis Pilaris, Skin Diseases, 030207 dermatology & venereal diseases, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Medicine, Humans, Prospective Studies, skin and connective tissue diseases, Child, Genetic Association Studies, ComputingMilieux_MISCELLANEOUS, Aged, Univariate analysis, Mutation, business.industry, Noonan Syndrome, Multiple Lentigines, Infant, Middle Aged, medicine.disease, 3. Good health, PTPN11, medicine.anatomical_structure, Phenotype, Scalp, Child, Preschool, Noonan syndrome, Female, business
Abstract: BACKGROUND Data on dermatological manifestations of Noonan syndrome (NS) remain heterogeneous and are based on limited dermatological expertise. OBJECTIVES To describe the dermatological manifestations of NS, compare them with the literature findings, and test for dermatological phenotype-genotype correlations with or without the presence of PTPN11 mutations. METHODS We performed a large 4-year, prospective, multicentric, collaborative dermatological and genetic study. RESULTS Overall, 129 patients with NS were enrolled, including 65 patients with PTPN11-NS, 34 patients with PTPN11-NS with multiple lentigines (NSML), and 30 patients with NS who had a mutation other than PTPN11. Easy bruising was the most frequent dermatological finding in PTPN11-NS, present in 53·8% of patients. Multiple lentigines and cafe-au-lait macules (n ≥ 3) were present in 94% and 80% of cases of NSML linked to specific mutations of PTPN11, respectively. Atypical forms of NSML could be associated with NS with RAF1 or NRAS mutations. In univariate analysis, patients without a PTPN11 mutation showed (i) a significantly higher frequency of keratinization disorders (P = 0·001), including keratosis pilaris (P = 0·005), ulerythema ophryogenes (P = 0·0001) and palmar and/or plantar hyperkeratosis (P = 0·06, trend association), and (ii) a significantly higher frequency of scarce scalp hair (P = 0·035) and scarce or absent eyelashes (P = 0·06, trend association) than those with PTPN11 mutations. CONCLUSIONS The cutaneous phenotype of NS with a PTPN11 mutation is generally mild and nonspecific, whereas the absence of a PTPN11 mutation is associated with a high frequency of keratinization disorders and hair abnormalities.
Published: 2019

13. Psoriatic arthritis screening by the dermatologist: development and first validation of the 'PURE-4 scale'

Author: M. Bagot, D. Lons Danic, Etienne Audureau, Michel Richard, N. Gouyette, F. Roux, Alain Cantagrel, E. Dernis, Denis Jullien, Pascal Claudepierre, Thierry Passeron, P. Hilliquin, Frédéric Lioté, Laboratoire d'Investigation Clinique (LIC), Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), L'Oréal Recherche France (L'Oréal Recherche), L'OREAL, Centre Hospitalier Universitaire de Purpan (CHU Purpan), Service de Rhumatologie [CH Le Mans], Centre Hospitalier Le Mans (CH Le Mans), Centre Hospitalier Sud Francilien, Service de dermatologie, consultation d'allergologie, Hôpital Edouard-Herriot, Hôpital Edouard Herriot [CHU - HCL], Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Biologie de l'Os et du Cartilage : Régulations et Ciblages Thérapeutiques (BIOSCAR (UMR_S_1132 / U1132)), Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Dermatologie [Nice], Hôpital Archet 2 [Nice] (CHU), Inserm U1065, Centre Méditerranéen de Médecine Moléculaire, Service de rhumatologie [CHU Henri Mondor], and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor
Subjects: Male, MESH: Logistic Models, MESH: Risk Assessment, Severity of Illness Index, Dactylitis, Cohort Studies, 030207 dermatology & venereal diseases, 0302 clinical medicine, MESH: Early Diagnosis, Mass Screening, MESH: Arthritis, Psoriatic, MESH: Incidence, MESH: Cohort Studies, MESH: Program Evaluation, MESH: Psoriasis, MESH: Middle Aged, Incidence, MESH: Sex Distribution, Middle Aged, MESH: Predictive Value of Tests, Infectious Diseases, Joint pain, Predictive value of tests, Area Under Curve, Female, France, medicine.symptom, Cohort study, Adult, medicine.medical_specialty, Dermatology, Risk Assessment, 03 medical and health sciences, Psoriatic arthritis, Age Distribution, Predictive Value of Tests, Psoriasis, MESH: Severity of Illness Index, medicine, Humans, MESH: Mass Screening, Sex Distribution, MESH: Age Distribution, Retrospective Studies, 030203 arthritis & rheumatology, MESH: Humans, business.industry, Arthritis, Psoriatic, Retrospective cohort study, MESH: Adult, MESH: Retrospective Studies, MESH: ROC Curve, medicine.disease, Triage, MESH: Male, MESH: Dermatologists, MESH: France, Early Diagnosis, Logistic Models, ROC Curve, MESH: Area Under Curve, business, MESH: Female, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology, Dermatologists, Program Evaluation
Abstract: BACKGROUND Dermatologists are recommended to ask psoriasis patients about musculoskeletal complaints to allow early detection and treatment of psoriatic arthritis (PsA). Screening tools have been developed to help identify patients warranting further rheumatologic assessment, but evidence suggests room for improvement in their diagnostic value and ease of use for outpatient practice. OBJECTIVE To develop and internally validate a brief tool for dermatologists to screen patients to refer to a rheumatologist for PsA diagnosis. METHODS After the literature review, 23 items were selected, covering pain at various locations and inflammatory signs of PsA. The validation study was conducted in medically diagnosed psoriasis patients consecutively recruited between 2012 and 2014 (Saint Joseph Hospital, Paris, France). Patients were enrolled by a dermatologist who helped to complete the questionnaire. Diagnosis of PsA was established by a rheumatologist based on CASPAR criteria. Multivariate logistic regression models were performed to build the scale, assessing discrimination through sensitivity, specificity and area under the ROC curve (AUC). Final model was internally validated using bootstrapping techniques. RESULTS One hundred and sixty-eight patients were recruited, of whom nine were excluded for known PsA and 21 did not attend the rheumatologist consultation. Of 137 included patients (median age 43 years, 59.6% men), 21 (15.3%) had a PsA diagnosis. Final regression model retained four independent items, including evocative signs of dactylitis, inflammatory heel pain, bilateral buttock pain and peripheral joint pain with swelling in patients aged
Published: 2018

14. Deux nouveaux cas (Two new cases)

Author: Severino-Freire, M., Bing Lecointe, A.-C., Bourrat, E., Pichery, M., Jonca, N., Chiaverini, C., Mazereeuw-Hautier, J., CHU Toulouse [Toulouse], Hôpital d'Annecy, Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Unité différenciation épidermique et auto-immunité rhumatoïde (UDEAR), 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), Service de Dermatologie [Nice], and Hôpital Archet 2 [Nice] (CHU)
Subjects: Polyhydramnios, MESH: Infant, Premature, Diseases / pathology, MESH: Ichthyosis / diagnosis, Syndrome « ichtyose-prématurité », MESH: Exons / genetics, Fatty acid transporter protein 4, Vital risk, Détresse respiratoire, FATP4, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, MESH: Gestational Age, MESH: Ichthyosis / complications, MESH: Point Mutation, MESH: Heterozygote, MESH: Consanguinity, MESH: Mutation, Missense, MESH: Infant, Premature, Diseases / diagnosis, MESH: Humans, MESH: Remission, Spontaneous, MESH: Ichthyosis / pathology, MESH: Infant, Newborn, MESH: Infant, Premature, Diseases / genetics, Respiratory distress, MESH: Male, MESH: Respiratory Distress Syndrome, Newborn / complications, MESH: Fatty Acid Transport Proteins / genetics, Ichthyosis prematurity syndrome, Risque vital, MESH: Ichthyosis / genetics
Abstract: International audience; Background: Ichthyosis prematurity syndrome is a rare syndromic form of ichthyosis caused by mutations in FATP4, which plays a central role in the transport and activation of fatty acids in the epidermis and in epidermal barrier function. Despite stereotypical clinical presentation in the neonatal period, the diagnosis is not well known by clinicians. Herein we report two new cases. Patients and methods: Case no. 1: a boy born prematurely (33weeks of gestation) to non-consanguineous French parents presented at birth with respiratory distress necessitating admission to intensive care. His skin was covered by a thick caseous vernix, especially on the scalp, eyebrows and 4 limbs. At the age of 4years, the boy's skin appeared normal. Case no. 2: a boy born prematurely to consanguineous Moroccan parents (34weeks of gestation) presented at birth with respiratory distress requiring admission to intensive care. At clinical examination, he had a whitish thick skin giving an impression of vernix caseosa, with involvement of the scalp, forehead, 4 limbs and abdomen. At the age of 2 years, his skin was normal. Conclusion: The clinical presentation of this syndrome is typical. It is important to make the diagnosis to enable genetic counseling and planning of adequate neonatal care in the event of future pregnancies.; Introduction : Le « syndrome ichtyose-prématurité » est très rare ; il appartient au groupe des ichtyoses syndromiques. Il est dû à des mutations du gène FATP4, lequel joue un rôle clé dans le transport et l’activation des acides gras de l’épiderme et dans la fonction barrière cutanée. Malgré une présentation clinique stéréotypée en période néonatale, l’affection est peu connue des cliniciens. Nous en rapportons deux nouveaux cas.Observations Cas no 1 : il s’agissait d’un enfant de sexe masculin, d’origine française, né de parents non apparentés à 33 semaines de gestation. À la naissance, l’enfant présentait une détresse respiratoire prise en charge en réanimation néonatale. Sur le plan cutané, on notait un aspect de vernix caseosa épais atteignant principalement le cuir chevelu, les sourcils et les quatre membres. L’évolution était favorable, avec un examen cutané normal à 4 ans. Cas no 2 : il s’agissait d’un enfant de sexe masculin, d’origine marocaine, né de parents apparentés à 34 semaines de gestation. À la naissance, il présentait une détresse respiratoire aiguë prise en charge en réanimation néonatale. À l’examen clinique, il avait un aspect épaissi de la peau mimant un vernix caseosa, blanchâtre, localisé principalement sur le cuir chevelu, le front, les quatre membres et l’abdomen. L’évolution était favorable, avec un examen cutané normal à 2 ans.Conclusion : Nos deux patients illustrent la présentation clinique caractéristique de ce syndrome, qui mérite d’être connu des cliniciens pédiatres et dermatologues afin de poser le diagnostic, de réaliser un conseil génétique et de prévoir une prise en charge adaptée de la période périnatale en cas de future grossesse.
Published: 2018

15. Tongue psoriasis: Clinical aspects and analysis of epidemiological associations in 313 children, with a systematic literature review

Author: Groupe de Recherche de la Société Française de Dermatologie Pédiatrique, Pierre Vabres, E. Mahé, D. Pourchot, C Droicourt, I. Kupfer-Bessaguet, Sébastien Barbarot, Maryam Piram, Xavier Balguerie, A. Beauchet, Emmanuelle Bourrat, Eve Puzenat, Anne-Claire Bursztejn, M. Ferneiny, Thomas Hubiche, Christine Chiaverini, Service de Dermatologie et pathologies vasculaires [CH Argenteuil], Centre Hospitalier Victor Dupouy, Service de Dermatologie [Nice], Hôpital Archet 2 [Nice] (CHU), Service de Pédiatrie Générale du Pr. A. Faye, Hopital Robert Debré (APHP), Université Paris Diderot - Paris 7 (UPD7), Service de dermatologie [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Dermatologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Intercommunal Fréjus - St Raphaël (CHI Fréjus - St Raphaël), Service de Dermatologie [Rennes] = Dermatology [Rennes], CHU Pontchaillou [Rennes], Service d’Hématologie et Rhumatologie Pédiatrique [AP-HP Hôpital Bicêtre], Centre de Référence Maladies constitutionnelles du Globule rouge [AP-HP Hôpital Bicêtre]-AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre), Service de Dermatologie et Vénérologie [Hôpital Laënnec, site de Quimper], CH Cornouaille, Service de dermatologie (Centre Hospitalier de Niort), Centre Hospitalier Georges Renon [Niort] (CH Georges Renon Niort), Service de dermatologie [CHU Necker], CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de dermatologie (CHRU Besançon), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service de Dermatologie [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-Hôpital Charles Nicolle [Rouen], AP-HP, Hôpital Ambroise Paré, Unité de Recherche Clinique et Département de Santé Publique, Service de Dermatologie et Allergologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), AP-HP Hôpital Bicêtre (Le Kremlin-Bicêtre)-Centre de Référence Maladies constitutionnelles du Globule rouge [AP-HP Hôpital Bicêtre], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département de dermatologie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Hôpital Saint-Jacques-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Hôpital Charles Nicolle [Rouen]-CHU Rouen, and Normandie Université (NU)-Normandie Université (NU)
Subjects: Male, Enfant, medicine.medical_specialty, Pediatric Obesity, Glossitis, Adolescent, Nourrisson, prevalence, Dermatology, Comorbidity, Tongue Diseases, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Tongue, Risk Factors, Psoriasis, Epidemiology, medicine, Humans, Tongue, Fissured, Child, mucosa, childhood psoriasis, business.industry, Infant, 030206 dentistry, Benign Migratory Glossitis, medicine.disease, Glossitis, Benign Migratory, 3. Good health, Geographic tongue, Systematic review, medicine.anatomical_structure, Cross-Sectional Studies, Child, Preschool, oral lesions, Langue, Female, France, business, Fissured tongue, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology
Abstract: IF 1,051 (2018); International audience; Background. - Little information is available on the prevalence and clinical aspects of tongue involvement in children with psoriasis. The aim was to evaluate the prevalence, clinical aspects and risk factors concerning tongue involvement in children with psoriasis.Patients and methods. - This study was carried out in two stages. We performed a multicentre, cross-sectional study in 23 French dermatology centers. All children seen for psoriasis during the one-year study were systematically included. The clinical features of the tongue and of psoriasis were recorded. Association with clinical aspects of psoriasis and comorbidities was evaluated. We then carried out a literature review to evaluate the prevalence of tongue involvement in children with psoriasis and its positive predictive value for psoriasis. A search was conducted in the PUBMED database using the following keywords: "child'' and "psoriasis'' and ("tongue'' or "glossitis'' or "migratory glossitis'' or "benign migratory glossitis'' or "geographic tongue'' or "fissured tongue'').Results. - 7.7% of the 313 children with psoriasis had tongue involvement. The clinical aspects were geographic tongue (4.2%), fissured tongue (2.8%) and both (0.64%). There was no association between tongue involvement and the clinical characteristics of the children. Two hundred and ninety-five articles were referenced and 3 were analysed. Psoriasis is very rare in cases of tongue abnormalities.Conclusion. - The prevalence of tongue involvement was 7.7% in children with psoriasis. No clinical or epidemiological association was shown. Tongue involvement does not modify the management of psoriasis. In the literature review it was not possible to evaluate either the prevalence of tongue involvement in psoriasis or the positive predictive value thereof.; IntroductionIl y a peu d’informations dans la littérature sur les atteintes de la langue au cours du psoriasis de l’enfant. L’objectif était d’évaluer la fréquence, les aspects cliniques et les facteurs de risque d’atteinte linguale chez les enfants psoriasiques.Patients et méthodesCe travail a été effectué en deux étapes : (1) une étude transversale a été menée dans 23 centres dermatologiques français, notant les aspects cliniques de la langue et du psoriasis chez les enfants atteints de psoriasis, ainsi que les associations et les comorbidités ; (2) une revue systématique de la littérature a ensuite été effectuée afin d’évaluer la prévalence l’atteinte linguale chez l’enfant et sa valeur prédictive du psoriasis. Une recherche a été réalisée en interrogeant la base de données PUBMED. Les mots clés saisis étaient : « child » et « psoriasis » et (« tongue » ou « glossitis » ou « migratory glossitis » ou « benign migratory glossitis » ou « geographic tongue » ou « fissured tongue »).Résultats(1) Parmi 313 enfants atteints de psoriasis 7,7 % présentaient une atteinte linguale sous forme de langue géographique (4,2 %), langue fissurée (2,8 %) ou les deux (0,6 %). L’atteinte linguale n’était associée à aucune particularité démographique ou clinique, ni aucune comorbidité. (2) Parmi 295 articles référencés, 3 ont finalement été retenus. Le psoriasis reste très rare en cas d’anomalie linguale.ConclusionLa prévalence de l’atteinte linguale chez les enfants psoriasiques était de 7,7 %. Aucune association clinique ou épidémiologique n’a été montrée. L’atteinte linguale ne modifie pas la prise en charge du psoriasis. La revue systématique de la littérature ne permettait pas d’évaluer une prévalence de l’atteinte linguale dans le psoriasis ni la valeur prédictive positive de cette atteinte.
Published: 2018

16. Treatment of voluminous and complicated superficial slow-flow vascular malformations with sirolimus (PERFORMUS): protocol for a multicenter phase 2 trial with a randomized observational-phase design

Author: Valérie Gissot, Laurent Guibaud, Groupe de Recherche de la Société Française de Dermatologie Pédiatrique, Jean-Baptiste Woillard, Christine Chiaverini, Sébastien Barbarot, Catherine Droitcourt, Stéphanie Mallet, Bruno Giraudeau, Juliette Mazereeuw-Hautier, Dominique Goga, Ludovic Martin, Gérard Lorette, Jérôme Rollin, Denis Herbreteau, Didier Bessis, Yves Gruel, Baptiste Morel, Annabel Maruani, Sophie Leducq, Annie-Pierre Jonville-Béra, Anne Le Touze, Elsa Tavernier, Pierre Vabres, Olivia Boccara, Sophie Blaise, MethodS in Patients-centered outcomes and HEalth ResEarch (SPHERE), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Service de dermatologie (CHRU de Tours), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Clinical Investigation Center - INSERM 1415, CHU Necker - Enfants Malades [AP-HP], Centre de Référence National des Maladies Génétiques à Expression Cutanée (MAGEC), Service de Dermatologie, Département de dermatologie [CHU de Montpellier], Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Service de Dermatologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de dermatologie (CHU de Toulouse), CHU Toulouse [Toulouse], Service de dermatologie [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Dermatologie [Nice], Hôpital Archet 2 [Nice] (CHU), Clinique de Médecine Vasculaire, Université Joseph Fourier - Grenoble 1 (UJF)-CHU Grenoble, Service de Dermatologie [Rennes], CHU Pontchaillou [Rennes], Département de dermatologie, CHU Marseille, CHU Marseille, Service de Dermatologie [CHU Angers] (PXE - le PseudoXanthome Elastique), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Service de pharmacologie clinique [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Groupe innovation et ciblage cellulaire (GICC), EA 7501 [2018-...] (GICC EA 7501), Université de Tours, Service de neuroradiologie [Tours], Service de chirurgie maxillo-faciale [CHRU Tours], Département de chirurgie pédiatrique [Clocheville University Hospital, Tours], CHRU Clocheville, CIC 1415 Centre d’Investigation Clinique, Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Radiologie [CHU Trousseau], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Trousseau [APHP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Sorbonne Université-Sorbonne Université, Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Centre d’Investigation Clinique [Tours] CIC 1415 (CIC ), Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de dermatologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL), CHU Dijon, Centre Hospitalier Universitaire [Grenoble] (CHU), PRES Université Nantes Angers Le Mans (UNAM), Pharmacologie des Immunosuppresseurs et de la Transplantation (PIST), Institut National de la Santé et de la Recherche Médicale (INSERM)-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Université de Limoges (UNILIM)-CHU Limoges, Université de Tours (UT), Groupe de Recherche de la Societé Française de Dermatologie Pédiatrique., Rollin, Jérôme, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Université de Limoges (UNILIM)-CHU Limoges-Génomique, Environnement, Immunité, Santé, Thérapeutique (GEIST FR CNRS 3503)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)-Hôpital Bretonneau-Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Male, Pediatrics, Time Factors, Vascular Malformations, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Medicine (miscellaneous), Study Protocol, 0302 clinical medicine, Quality of life, Sclerotherapy, Clinical endpoint, Multicenter Studies as Topic, Pharmacology (medical), Child, Lymphatic malformations, Children, Mammalian target of rapamycin inhibitors, Randomized Controlled Trials as Topic, lcsh:R5-920, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, Age Factors, Vascular anomalies, Magnetic Resonance Imaging, 3. Good health, Lymphangiogenesis, Natural history, [SDV] Life Sciences [q-bio], Observational Studies as Topic, Treatment Outcome, 030220 oncology & carcinogenesis, Venous malformations, Female, France, lcsh:Medicine (General), Blood Flow Velocity, medicine.drug, medicine.medical_specialty, Adolescent, 03 medical and health sciences, Clinical Trials, Phase II as Topic, 030225 pediatrics, Coronary Circulation, medicine, Humans, Protein Kinase Inhibitors, Sirolimus, business.industry, Clinical trial, Randomized placebo-phase design, Observational study, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Background Slow-flow superficial vascular malformations (VMs) are rare congenital anomalies that can be responsible for pain and functional impairment. Currently, we have no guidelines for their management, which can involve physical bandages, sclerotherapy, surgery, anti-inflammatory or anti-coagulation drugs or no treatment. The natural history is progressive and worsening. Mammalian target of rapamycin (mTOR) is a serine/threonine kinase that acts as a master switch in cell proliferation, apoptosis, metabolism and angio/lymphangiogenesis. Sirolimus directly inhibits the mTOR pathway, thereby inhibiting cell proliferation and angio/lymphangiogenesis. Case reports and series have reported successful use of sirolimus in children with different types of vascular anomalies, with heterogeneous outcomes. Objective The objective of this trial is to evaluate the efficacy and safety of sirolimus in children with complicated superficial slow-flow VMs. Methods/design This French multicenter randomized observational-phase, phase 2 trial aims to include 50 pediatric patients 6 to 18 years old who have slow-flow (lymphatic, venous or lymphatico-venous) voluminous complicated superficial VM. Patients will be followed up for 12 months. All patients will start with an observational period (no treatment). Then at a time randomly selected between month 4 and month 8, they will switch to the experimental period (switch time), when they will receive sirolimus until month 12. Each child will undergo MRI 3 times: at baseline, at the switch time, and at month 12. For both periods (observational and treatment), we will calculate the relative change in volume of the VM divided by the study period duration. This relative change weighted by the study period duration will constitute the primary endpoint. VM will be measured by MRI images, which will be centralized and interpreted by the same radiologist who will be blinded to the study period. Hence, each patient will be his/her own control. Secondary outcomes will include assessment of safety and efficacy by viewing standardized digital photographs and according to the physician, the patient or proxy; impact on quality of life; and evolution of biological makers (coagulation factors, vascular endothelial growth factor, tissue factor). Discussion The main benefit of the study will be to resolve uncertainty concerning the efficacy of sirolimus in reducing the volume of VMs and limiting related complications and the safety of the drug in children with slow-flow VMs. This trial design is interesting in these rare conditions because all included patients will have the opportunity to receive the drug and the physician can maintain it after the end of the protocol if is found efficient (which would not be the case in a classical cross-over study). Trial registration ClinicalTrials.gov Identifier: NCT02509468, first received: 28 July 2015. EU Clinical Trials Register EudraCT Number: 2015-001096-43. Electronic supplementary material The online version of this article (10.1186/s13063-018-2725-1) contains supplementary material, which is available to authorized users.
Published: 2018

17. Epidermolysis bullosa simplex generalized severe induces a Th17 response and is improved by Apremilast treatment

Author: E. Castela, Christine Chiaverini, Frédéric Bérard, Fanny Morice-Picard, J.-P. Lacour, Didier Bessis, Jean-François Nicolas, Aurore Rozières, Meri K. Tulic, D. Baty, Jean Kanitakis, Pierre Vabres, J. Mazereeuw, Thierry Passeron, Emmanuelle Bourrat, Service de Dermatologie [Nice], Hôpital Archet 2 [Nice] (CHU), Immunologie de l'allergie cutanée et vaccination – Immunology of skin allergy and vaccination, Centre International de Recherche en Infectiologie (CIRI), École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure de Lyon (ENS de Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Université Jean Monnet - Saint-Étienne (UJM)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Inserm U1065, Centre Méditerranéen de Médecine Moléculaire, Centre de référence national des Maladies Génétiques à Expression Cutanée - National Reference Center for Genodermatoses and Rare Skin Diseases (MAGEC), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département d'allergie et d'immunologie clinique [CHU Lyon Sud], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), Département de Dermatologie [CH Lyon-Sud, Pierre-Bénite], Infections Virales et Pathologie Comparée - UMR 754 (IVPC), Institut National de la Recherche Agronomique (INRA)-École Pratique des Hautes Études (EPHE), Université Paris sciences et lettres (PSL)-Université Paris sciences et lettres (PSL)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon, Service de Dermatologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Département de dermatologie [CHU de Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), CHU Bordeaux [Bordeaux], Ninewells Hospital and Medical School [Dundee], Centre de Référence des Epidermolyses Bulleuses Héréditaires [Nice] (CREBHN), Centre Hospitalier Universitaire de Nice (CHU Nice), Centre International de Recherche en Infectiologie - UMR (CIRI), École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-École normale supérieure - Lyon (ENS Lyon)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Centre de référence national des Maladies Génétiques à Expression Cutanée (MAGEC), CHU Necker - Enfants Malades [AP-HP]-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Institut National de la Recherche Agronomique (INRA)-École pratique des hautes études (EPHE)-Université Claude Bernard Lyon 1 (UCBL), Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), CHU Toulouse [Toulouse], Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], and Institut National de la Recherche Agronomique (INRA)-École pratique des hautes études (EPHE)
Subjects: Adult, Male, Pathology, medicine.medical_specialty, Inflammation, Pilot Projects, Dermatology, Pathogenesis, 030207 dermatology & venereal diseases, 03 medical and health sciences, Epidermolysis bullosa simplex, Young Adult, 0302 clinical medicine, medicine, CXCL10, Humans, Child, Retrospective Studies, Skin, integumentary system, business.industry, Anti-Inflammatory Agents, Non-Steroidal, Infant, Newborn, Keratin-14, Infant, Middle Aged, medicine.disease, [SDV.MP.BAC]Life Sciences [q-bio]/Microbiology and Parasitology/Bacteriology, 3. Good health, Thalidomide, Treatment Outcome, Child, Preschool, Epidermolysis Bullosa Simplex, Mutation, [SDV.MP.VIR]Life Sciences [q-bio]/Microbiology and Parasitology/Virology, CXCL9, Keratin-5, Th17 Cells, [SDV.IMM]Life Sciences [q-bio]/Immunology, Female, Apremilast, medicine.symptom, business, Infiltration (medical), Immunostaining, medicine.drug
Abstract: International audience; BACKGROUND: Epidermolysis bullosa simplex generalized severe is a genetic disorder caused by mutation in KRT5 or KRT14 genes. Usually considered as a mechanical disease, recent data argue for additional inflammatory mechanisms. OBJECTIVES: The aim of this study was to assess the inflammation in the skin of patients with EBS. METHODS: A first immunohistochemical retrospective study was performed on frozen skin samples from 17 EBS-gen sev patients. A second multicenter prospective study was conducted on 10 patients with severe EBS-gen sev. Blister fluid and epidermis were processed for immunochemistry analysis and quantitative real time PCR. Cytokine expression was analyzed in blister fluid and compared with controls. RESULTS: Histological analysis showed a constant dermal perivascular CD4+ lymphocytes infiltrate in skin biopsies of blister (n=17) as well as in rubbed skin (n=5), an epidermal infiltration of neutrophils and eosinophils in 70% of cases and an increased immunostaining for CXCL9 and CXCL10 in blistering skin. High levels of Th17 cytokines were detected in lesional skin. Three adult patients with EBS-gen sev were treated with apremilast with a dramatic improvement of skin blistering and good tolerance. CONCLUSION: Our study demonstrates the importance of inflammation in EBS-gen sev patients and underlines the key role for Th17 cells in its pathogenesis. In addition, this study provides promising new therapeutic approaches for this disabling disorder. This article is protected by copyright. All rights reserved.
Published: 2018

18. Update of survival and cost of metastatic melanoma with new drugs: Estimations from the MelBase cohort

Author: Bernard Guillot, Philippe Saiag, M.-T. Leccia, Florence Granel-Brocard, Federico Rotolo, Eve Maubec, Céleste Lebbé, M. Kandel, Thierry Lesimple, Isabelle Borget, A. Ballon, F. Brunet-Possenti, J.-J. Grob, Jean-Philippe Arnault, Stéphane Dalle, D. Legoupil, Clara Allayous, C. Dutriaux, J.-P. Lacour, P.-E. Stoebner, Marie Beylot-Barry, F. Aubin, B. Dréno, Laurent Mortier, Sophie Dalac, Alain Dupuy, Stefan Michiels, Institut Gustave Roussy (IGR), Service de biostatistique et d'épidémiologie (SBE), Direction de la recherche clinique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Hôpital Claude Huriez [Lille], CHU Lille, Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), CHU Bordeaux [Bordeaux], CHU Grenoble, Pathogénèse et contrôle des infections chroniques (PCCI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Service de Dermatologie [Nice], Hôpital Archet 2 [Nice] (CHU), Physiopathologie du cancer du foie, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Dermatologie et Allergologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), CHU Pontchaillou [Rennes], 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), Service de Dermatologie [AP-HP Hôpital Saint-Louis], Hopital Saint-Louis [AP-HP] (AP-HP), and Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: Adult, Male, Cancer Research, medicine.medical_specialty, Metastatic melanoma, Survival, Total cost, Cost, medicine.medical_treatment, [SDV]Life Sciences [q-bio], Cost-Benefit Analysis, Antineoplastic Agents, Disease, Kaplan-Meier Estimate, Drug Costs, Targeted therapy, Cohort Studies, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Internal medicine, medicine, Humans, 030212 general & internal medicine, Molecular Targeted Therapy, Prospective Studies, Hospital Costs, Melanoma, Aged, Aged, 80 and over, business.industry, Therapies, Investigational, Real-life clinical practiceImmunotherapy, Immunotherapy, Health Care Costs, Middle Aged, 3. Good health, Radiation therapy, Survival Rate, Oncology, 030220 oncology & carcinogenesis, Financial sustainability, Cohort, Female, France, business
Abstract: International audience; Purpose Since 2011, significant progress was observed in metastatic melanoma (MM), with the commercialisation of seven immunotherapies or targeted therapies, which showed significant improvement in survival. In France, in 2004, the cost of MM was estimated at €1634 per patient; this cost has not been re-estimated since. This study provided an update on survival and cost in real-life clinical practice. Methods Clinical and economic data (treatments, hospitalisations, radiotherapy sessions, visits, imaging and biological exams) were extracted from the prospective MelBase cohort, collecting individual data in 955 patients in 26 hospitals, from diagnosis of metastatic disease until death. Survival was estimated by the Kaplan-Meier method. Costs were calculated from the health insurance perspective using French tariffs. For live patients, survival and costs were extrapolated using a multistate model, describing the 5-year course of the disease according to patient prognostic factors and number of treatment lines. Results Since the availability of new drugs, the mean survival time of MM patients has increased to 23.6 months (95%confidence interval [CI] :21.2;26.6), with 58% of patients receiving a second line of treatment. Mean management costs increased to €269,682 (95%CI:244,196;304,916) per patient. Drugs accounted for 80% of the total cost. Conclusion This study is the first that evaluated the impact of immunotherapies and targeted therapies both on survival and cost in real-life conditions. Alongside the introduction of breakthrough therapies in the first and subsequent lines, MM has been associated with a significant increase in survival but also in costs, raising the question of financial sustainability.
Published: 2018

19. Lysosomal acid ceramidase ASAH1 controls the transition between invasive and proliferative phenotype in melanoma cells

Author: Nicolas Nottet, Stéphane Dalle, Robert Ballotti, Julie Caramel, Céline Gaudel, Virginie Garcia, Karine Bille, Garance Tondeur, Corine Bertolotto, Justine Leclerc, Charlotte Pandiani, Pascal Colosetti, Philippe Bahadoran, David Garandeau, Sophie Pagnotta, Nathalie Andrieu-Abadie, Baharia Mograbi, Thierry Levade, Ethnologie préhistorique, Archéologies et Sciences de l'Antiquité (ArScAn), Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris Nanterre (UPN)-Ministère de la Culture et de la Communication (MCC)-Centre National de la Recherche Scientifique (CNRS)-Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris Nanterre (UPN)-Ministère de la Culture et de la Communication (MCC)-Centre National de la Recherche Scientifique (CNRS), Unité mixte de physique CNRS/Thales (UMPhy CNRS/THALES), Centre National de la Recherche Scientifique (CNRS)-THALES, Cardiovasculaire, métabolisme, diabétologie et nutrition (CarMeN), Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut National des Sciences Appliquées de Lyon (INSA Lyon), Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Institut National de la Recherche Agronomique (INRA), Centre Commun de Microscopie Appliquée (CCMA), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015 - 2019) (COMUE UCA), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Université Claude Bernard Lyon 1 (UCBL), Université de Lyon, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS)-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon], Centre méditerranéen de médecine moléculaire (C3M), 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)-Université Côte d'Azur (UCA), Centre de Recherches en Cancérologie de Toulouse (CRCT), 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), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université de Lyon-Institut National des Sciences Appliquées (INSA)-Université Claude Bernard Lyon 1 (UCBL), Centre Commun de Microscopie Appliquée [Nice] (CCMA), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Service de Dermatologie [Nice], Hôpital Archet 2 [Nice] (CHU), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Infection bactérienne, inflammation, et carcinogenèse digestive, COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-IFR50-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), ERI-21/EA 4319, Laboratoire de Pathologie Clinique et Expérimentale et CRB INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Louis Pasteur [Chartres]-Université de Nice Sophia-Antipolis (UNSA), This work was supported by Inserm, La Société Française de Dermatologie and by a grant from INCA (INCA_10573). CP is a fellowship from la Ligue Nationale contre le cancer., Université Panthéon-Sorbonne (UP1)-Université Paris Nanterre (UPN)-Institut national de recherches archéologiques préventives (Inrap)-Ministère de la Culture et de la Communication (MCC)-Centre National de la Recherche Scientifique (CNRS)-Université Panthéon-Sorbonne (UP1)-Université Paris Nanterre (UPN)-Institut national de recherches archéologiques préventives (Inrap)-Ministère de la Culture et de la Communication (MCC)-Centre National de la Recherche Scientifique (CNRS), Unité mixte de physique CNRS/Thalès (UMP CNRS/THALES), THALES-Centre National de la Recherche Scientifique (CNRS), Institut National de la Recherche Agronomique (INRA)-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)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Hospices Civils de Lyon (HCL), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA), Centre de Recherche en Cancérologie de Lyon (CRCL), Université de Lyon-Université de Lyon-Centre Léon Bérard [Lyon]-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Université Nice Sophia Antipolis (1965 - 2019) (UNS), Université de Lyon-Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Hospices Civils de Lyon (HCL)-Institut National de la Santé et de la Recherche Médicale (INSERM), and BERTOLOTTO-BALLOTTI, BERTOLOTTO-BALLOTTI
Subjects: 0301 basic medicine, Cell Proliferation/*genetics, Male, Cancer Research, Acid Ceramidase, [SDV]Life Sciences [q-bio], 0302 clinical medicine, Receptors, Melanoma, Regulation of gene expression, Tumor, Vitronectin/genetics, Microphthalmia-associated transcription factor, Phenotype, 3. Good health, Acid Ceramidase/*genetics, Gene Expression Regulation, Neoplastic, 030220 oncology & carcinogenesis, ASAH1, Female, Signal transduction, Signal Transduction, Proto-Oncogene Proteins B-raf, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Melanoma/*genetics/pathology, Cell Line, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cell Line, Tumor, Genetics, medicine, Humans, Neoplasm Invasiveness, Receptors, Vitronectin, Molecular Biology, Cell Proliferation, Neoplastic, Microphthalmia-Associated Transcription Factor, medicine.disease, Focal Adhesion Kinase 1/genetics, 030104 developmental biology, Gene Expression Regulation, Cell culture, Focal Adhesion Kinase 1, Cancer research, Neoplasm Invasiveness/genetics, Microphthalmia-Associated Transcription Factor/*genetics
Abstract: International audience; Phenotypic plasticity and subsequent generation of intratumoral heterogeneity underly key traits in malignant melanoma such as drug resistance and metastasis. Melanoma plasticity promotes a switch between proliferative and invasive phenotypes characterized by different transcriptional programs of which MITF is a critical regulator. Here, we show that the acid ceramidase ASAH1, which controls sphingolipid metabolism, acted as a rheostat of the phenotypic switch in melanoma cells. Low ASAH1 expression was associated with an invasive behavior mediated by activation of the integrin alphavbeta5-FAK signaling cascade. In line with that, human melanoma biopsies revealed heterogeneous staining of ASAH1 and low ASAH1 expression at the melanoma invasive front. We also identified ASAH1 as a new target of MITF, thereby involving MITF in the regulation of sphingolipid metabolism. Together, our findings provide new cues to the mechanisms underlying the phenotypic plasticity of melanoma cells and identify new anti-metastatic targets.
Published: 2018

20. Childhood chronic prurigo: Interest in patch tests and delayed-reading skin prick tests to environmental allergens

Author: Maryam Piram, Anne-Claire Bursztejn, Audrey Lasek, Martin Perromat, Didier Bessis, Jin Ho Chong, Ludovic Martin, Alain Taïeb, Claire Maridet, Christine Chiaverini, Julien Seneschal, A. Phan, Franck Boralevi, C. Abasq, Bérénice Bréchat, J. Miquel, Université de Bordeaux (UB), CHU Sud Saint Pierre [Ile de la Réunion], Service de Dermatologie [Nice], Hôpital Archet 2 [Nice] (CHU), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Hôpital Saint Vincent de Paul de Lille, Groupe Hospitalier de l'Institut Catholique de Lille (GHICL), Service de Pédiatrie Générale et Rhumatologie Pédiatrique, Université Paris-Sud - Paris 11 (UP11)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Service de Dermatologie et Allergologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de dermatologie (Dermato - BREST), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL), Physiopathologie Cardiovasculaire et Mitochondriale (MITOVASC), Université d'Angers (UA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Biothérapies des maladies génétiques et cancers, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), U1035 Centre de R ef erence pour les Maladies Rares de la Peau, Service de Dermatologie Adulte et Pédiatrique, Institut National de la Santé et de la Recherche Médicale (INSERM), Dermatologie pédiatrique - Bordeaux, and CHU Bordeaux [Bordeaux]
Subjects: medicine.medical_specialty, Chronic prurigo, business.industry, [SDV]Life Sciences [q-bio], Immunology, MEDLINE, Delayed diagnosis, medicine.disease, Dermatology, 3. Good health, Clinical trial, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Chronic disease, Multicenter study, Prurigo, Immunology and Allergy, Medicine, 030212 general & internal medicine, business, Prospective cohort study, ComputingMilieux_MISCELLANEOUS
Abstract: International audience
Published: 2018

21. Deciphering the Role of Oncogenic MITFE318K in Senescence Delay and Melanoma Progression

Author: Jean-François Ottavi, Brigitte Bressac-de Paillerets, Karine Bille, Gian Marco De Donatis, Guillaume Bossis, Thomas Strub, Mickaël Ohanna, Stéphane Rocchi, Jean-Philippe Lacour, Véronique Hofman, Irwin Davidson, Sandrine Marchetti, Yann Cheli, Marie-Christine Birling, Paul Hofman, Thomas Luc, Jean-Christophe Marine, Frederic Luciano, Fanélie-Marie Jouenne, Marina Boncompagni, Corine Bertolotto, Flavie Luciani, Marie-Françoise Avril, Caroline Bonet, Justine Leclerc, N. Poulalhon, Robert Ballotti, Centre méditerranéen de médecine moléculaire (C3M), 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 National de la Santé et de la Recherche Médicale (INSERM), Régulations cellulaires et oncogenèse (RCO), Institut Curie [Paris]-Centre National de la Recherche Scientifique (CNRS), Réponses cellulaires au microenvironnement et cancer, Institut National de la Santé et de la Recherche Médicale (INSERM), Institut Gustave Roussy (IGR), Biologie et pathologies des cellules mélanocytaires : de la pigmentation cutanée aux mélanomes, COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-IFR50-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), 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)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Institut de Génétique Moléculaire de Montpellier (IGMM), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM), AxesSim, Physiopathologie de la survie et de la mort cellulaire et infection virale, French National Infrastructure for Mouse Phenogenomics (PHENOMIN), Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département de Dermatologie [CH Lyon-Sud, Pierre-Bénite], Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL)-Hospices Civils de Lyon (HCL), ERI-21/EA 4319, Laboratoire de Pathologie Clinique et Expérimentale et CRB INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Louis Pasteur [Chartres]-Université de Nice Sophia-Antipolis (UNSA), Service de Dermatologie [Nice], Hôpital Archet 2 [Nice] (CHU), Institut de génétique et biologie moléculaire et cellulaire (IGBMC), Université Louis Pasteur - Strasbourg I-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Immunologie intégrative des tumeurs (UMR 1186), Université Paris-Sud - Paris 11 (UP11)-Institut Gustave Roussy (IGR)-Institut National de la Santé et de la Recherche Médicale (INSERM), Catholic University of Leuven - Katholieke Universiteit Leuven (KU Leuven), This work was funded by la Société Française de Dermatologie, Melanoma Research Alliance (MRA Team Science Award #269626), ANR-13-BSV1-0025-01 to RB, Fondation pour la Recherche Médicale, La Ville de Nice, Cancéropôle PACA to CB, INCa grant 2013-1-MELA-05 to BBdP, Grant Fondation Gustave Roussy 2009, No. PRI-2010-18 to BBdP, Grant 2011 ITMO-Plan Cancer to BBdP, ICGC No. 201102 to BBdP., ANR-13-BSV1-0025,MITF-SUMOcode,Role de la SUMOylation de MITF (Microphthalmia associated Transcription Factor) dans la pigmentation cutanée, et le développement des nævus.(2013), Université Nice Sophia Antipolis (1965 - 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)-Université Côte d'Azur (UCA), Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), BERTOLOTTO-BALLOTTI, BERTOLOTTO-BALLOTTI, and Blanc 2013 - Role de la SUMOylation de MITF (Microphthalmia associated Transcription Factor) dans la pigmentation cutanée, et le développement des nævus. - - MITF-SUMOcode2013 - ANR-13-BSV1-0025 - Blanc 2013 - VALID
Subjects: 0301 basic medicine, Senescence, Adult, Proto-Oncogene Proteins B-raf, Cancer Research, Skin Neoplasms, Primary Cell Culture, Endogeny, [SDV.CAN]Life Sciences [q-bio]/Cancer, Proximity ligation assay, Biology, Melanin, 03 medical and health sciences, Mice, Germline mutation, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cell Line, Tumor, medicine, Nevus, Animals, Humans, Melanoma, Cellular Senescence, Germ-Line Mutation, Aged, Microphthalmia-Associated Transcription Factor, integumentary system, PTEN Phosphohydrolase, Sumoylation, Middle Aged, medicine.disease, Microphthalmia-associated transcription factor, 3. Good health, body regions, Disease Models, Animal, 030104 developmental biology, Oncology, Cancer research, Melanocytes, Transcriptome
Abstract: International audience; BACKGROUND:MITF encodes an oncogenic lineage-specific transcription factor in which a germline mutation ( MITFE318K ) was identified in human patients predisposed to both nevus formation and, among other tumor types, melanoma. The molecular mechanisms underlying the oncogenic activity of MITF E318K remained uncharacterized.METHODS:Here, we compared the SUMOylation status of endogenous MITF by proximity ligation assay in melanocytes isolated from wild-type (n = 3) or E318K (n = 4) MITF donors. We also used a newly generated Mitf E318K knock-in (KI) mouse model to assess the role of Mitf E318K (n = 7 to 13 mice per group) in tumor development in vivo and performed transcriptomic analysis of the tumors to identify the molecular mechanisms. Finally, using immortalized or normal melanocytes (wild-type or E318K MITF, n = 2 per group), we assessed the role of MITF E318K on the induction of senescence mediated by BRAF V600E . All statistical tests were two-sided.RESULTS:We demonstrated a decrease in endogenous MITF SUMOylation in melanocytes from MITF E318K patients (mean of cells with hypoSUMOylated MITF, MITF E318K vs MITF WT , 94% vs 44%, difference = 50%, 95% CI = 21.8% to 67.2%, P = .004). The Mitf E318K mice were slightly hypopigmented (mean melanin content Mitf WT vs Mitf E318K/+ , 0.54 arbitrary units [AU] vs 0.36 AU, difference = -0.18, 95% CI = -0.36 to -0.007, P = .04). We provided genetic evidence that Mitf E318K enhances BRaf V600E -induced nevus formation in vivo (mean nevus number for Mitf E318K , BRaf V600E vs Mitf WT , BRaf V600E , 68 vs 44, difference = 24, 95% CI = 9.1 to 38.9, P = .006). Importantly, although Mitf E318K was not sufficient to cooperate with BRaf V600E alone in promoting metastatic melanoma, it accelerated tumor formation on a BRaf V600E , Pten-deficient background (median survival, Mitf E318K/+ = 42 days, 95% CI = 31 to 46 vs Mitf WT = 51 days, 95% CI = 50 to 55, P
Published: 2017

22. SIRT1 promotes proliferation and inhibits the senescence-like phenotype in human melanoma cells

Author: Irwin Davidson, Maryline Allegra, Robert Ballotti, Corine Bertolotto, Caroline Bonet, Philippe Bahadoran, Jean-Philippe Lacour, Mickaël Ohanna, Karine Bille, BERTOLOTTO-BALLOTTI, BERTOLOTTO-BALLOTTI, Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (1965 - 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)-Université Côte d'Azur (UCA), Institut de Génétique et de Biologie Moléculaire et Cellulaire (IGBMC), Université de Strasbourg (UNISTRA)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Dermatologie [Nice], Hôpital Archet 2 [Nice] (CHU), Université Nice Sophia Antipolis (... - 2019) (UNS), and COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM)
Subjects: Cell cycle checkpoint, endocrine system diseases, Blotting, Western, Cell, Fluorescent Antibody Technique, [SDV.CAN]Life Sciences [q-bio]/Cancer, Context (language use), Biology, Transfection, environment and public health, SIRT1, [SDV.CAN] Life Sciences [q-bio]/Cancer, Sirtuin 1, melanoma, medicine, Humans, RNA, Small Interfering, Cellular Senescence, Cell Proliferation, MITF, Microscopy, Confocal, treatment, Cell growth, Melanoma, Cancer, PLX4032, Microphthalmia-associated transcription factor, medicine.disease, Molecular biology, 3. Good health, enzymes and coenzymes (carbohydrates), Phenotype, medicine.anatomical_structure, Oncology, biological phenomena, cell phenomena, and immunity, Cell aging, hormones, hormone substitutes, and hormone antagonists, Research Paper
Abstract: // Mickael Ohanna 1,2 , Caroline Bonet 1,2 , Karine Bille 1,2 , Maryline Allegra 1,2 , Irwin Davidson 3 , Philippe Bahadoran 2,4 , Jean-Philippe Lacour 2,4 , Robert Ballotti 1,2 and Corine Bertolotto 1,2 . 1, INSERM, U1065 (equipe 1), Equipe labelisee Ligue Contre le Cancer, C3M, Nice, France. 2, Universite de Nice Sophia-Antipolis, UFR Medecine, Nice, France. 3, Institut de Genetique et de Biologie Moleculaire et Cellulaire, CNRS, INSERM, Universite de Strasbourg, Illkirch, France. 4, Centre Hospitalier Universitaire, Service de Dermatologie, Nice, France Correspondence: Corine Bertolotto, email: // Keywords : melanoma, MITF, SIRT1, PLX4032, treatment Received : February 7, 2014 Accepted :February 18, 2014 Published : February 19, 2014 Abstract SIRT1 operates as both a tumor suppressor and oncogenic factor depending on the cell context. Whether SIRT1 plays a role in melanoma biology remained poorly elucidated. Here, we demonstrate that SIRT1 is a critical regulator of melanoma cell proliferation. SIRT1 suppression by genetic or pharmacological approaches induces cell cycle arrest and a senescence-like phenotype. Gain and loss of function experiments show that M-MITF regulates SIRT1 expression, thereby revealing a melanocyte-specific control of SIRT1. SIRT1 over-expression relieves the senescence-like phenotype and the proliferation arrest caused by MITF suppression, demonstrating that SIRT1 is an effector of MITF -i nduced proliferation in melanoma cells. Interestingly, SIRT1 level and activity are enhanced in the PLX4032-resistant BRAF V600E -mutated melanoma cells compared with their sensitive counterpart. SIRT1 inhibition decreases melanoma cell growth and rescues the sensibility to PLX4032 of PLX4032-resistant BRAF V600E -mutated melanoma cells. In conclusion, we provide the first evidence that inhibition of SIRT1 warrants consideration as an anti-melanoma therapeutic option.
Published: 2014

23. Metformin Blocks Melanoma Invasion and Metastasis Development in AMPK/p53-Dependent Manner

Author: Mickaël Ohanna, Philippe Bahadoran, Sophie Tartare-Deckert, Mélanie Tichet, Patricia Abbe, Stéphane Rocchi, Corine Bertolotto, Michael Cerezo, Robert Ballotti, Abdelali Lehraiki, Florian Rouaud, Damien Giacchero, Maryline Allegra, Centre méditerranéen de médecine moléculaire (C3M), 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 National de la Santé et de la Recherche Médicale (INSERM), Service de Dermatologie [Nice], Hôpital Archet 2 [Nice] (CHU), BERTOLOTTO-BALLOTTI, BERTOLOTTO-BALLOTTI, Université Nice Sophia Antipolis (1965 - 2019) (UNS), and 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)-Université Côte d'Azur (UCA)
Subjects: Cancer Research, medicine.medical_specialty, Epithelial-Mesenchymal Transition, endocrine system diseases, [SDV.CAN]Life Sciences [q-bio]/Cancer, AMP-Activated Protein Kinases, Metastasis, Mice, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cell Movement, Cell Line, Tumor, Internal medicine, medicine, Animals, Humans, Neoplasm Invasiveness, Neoplasm Metastasis, Melanoma, 030304 developmental biology, 0303 health sciences, Chemistry, Metalloendopeptidases, AMPK, Cell migration, medicine.disease, Metformin, Extravasation, 3. Good health, Enzyme Activation, Disease Models, Animal, Endocrinology, Oncology, Cell culture, 030220 oncology & carcinogenesis, Cancer cell, Cancer research, Female, Tumor Suppressor Protein p53, medicine.drug
Abstract: Metformin was reported to inhibit the proliferation of many cancer cells, including melanoma cells. In this report, we investigated the effect of metformin on melanoma invasion and metastasis development. Using different in vitro approaches, we found that metformin inhibits cell invasion without affecting cell migration and independently of antiproliferation action. This inhibition is correlated with modulation of expression of proteins involved in epithelial–mesenchymal transition such as Slug, Snail, SPARC, fibronectin, and N-cadherin and with inhibition of MMP-2 and MMP-9 activation. Furthermore, our data indicate that this process is dependent on activation of AMPK and tumor suppressor protein p53. Finally, we showed that metformin inhibits melanoma metastasis development in mice using extravasation and metastasis models. The presented data reinforce the fact that metformin might be a good candidate for clinical trial in melanoma treatment. Mol Cancer Ther; 12(8); 1605–15. ©2013 AACR.
Published: 2013

24. Sinus aspergillosis due to an azole-resistant Aspergillus fumigatus strain carrying the TR34/L98H mutation in immunocompetent host

Author: M. Benassarou, Steffi Rocchi, Frédéric Grenouillet, Audrey Jeanvoine, Laurence Millon, Gabriel Reboux, Catherine Chirouze, Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service des maladies infectieuses et tropicales, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Hôpital Saint-Jacques, Université Nice Sophia Antipolis - Faculté de Médecine (UNS UFR Médecine), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Centre méditerranéen de médecine moléculaire (C3M), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Dermatologie [Nice], Hôpital Archet 2 [Nice] (CHU), Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Laboratoire Chrono-environnement ( LCE ), Université Bourgogne Franche-Comté ( UBFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ), Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ) -Hôpital Saint-Jacques, Université Nice Sophia Antipolis - Faculté de Médecine ( UNS UFR Médecine ), Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ), Centre méditérannéen de médecine moléculaire ( C3M ), Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Université Nice Sophia Antipolis ( UNS ), Hôpital Archet 2 [Nice] ( CHU ), and Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon )
Subjects: 0301 basic medicine, Microbiology (medical), 030106 microbiology, Drug resistance, Aspergillosis, Aspergillus fumigatus, Microbiology, [ SDV.EE.SANT ] Life Sciences [q-bio]/Ecology, environment/Health, 03 medical and health sciences, 0302 clinical medicine, medicine, Missense mutation, 030212 general & internal medicine, skin and connective tissue diseases, ComputingMilieux_MISCELLANEOUS, chemistry.chemical_classification, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, Fungal protein, General Immunology and Microbiology, biology, Strain (chemistry), business.industry, General Medicine, biology.organism_classification, medicine.disease, Infectious Diseases, chemistry, Mutation (genetic algorithm), Azole, business
Abstract: Sir,After a work-related accident, a woodworker developed sinusal aspergillosis due to an azole-resistant Aspergillus fumigatus strain carrying the TR34/L98H mutation. An environmental survey in tw...
Published: 2016

25. Assessment of pets (cats and dogs) in homes using electrostatic dust collectors and QPCR: new tools to evaluate exposure and risk of allergies

Author: Emeline Scherer, Gabriel Reboux, Sandrine Roussel, Laurence Millon, Mallory Vacheyrou, Benoît Valot, A. Naegele, Jenny Knapp, Steffi Rocchi, Laboratoire Chrono-environnement ( LCE ), Université Bourgogne Franche-Comté ( UBFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ), Université Nice Sophia Antipolis - Faculté de Médecine ( UNS UFR Médecine ), Université Nice Sophia Antipolis ( UNS ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ), Centre méditérannéen de médecine moléculaire ( C3M ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ), Service de Dermatologie [Nice], Hôpital Archet 2 [Nice] ( CHU ), Hôpital Jean Minjoz, Centre Hospitalier Régional Universitaire [Besançon] ( CHRU Besançon ), Laboratoire Chrono-environnement - CNRS - UBFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Université Nice Sophia Antipolis - Faculté de Médecine (UNS UFR Médecine), Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Centre méditerranéen de médecine moléculaire (C3M), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), and Hôpital Archet 2 [Nice] (CHU)
Subjects: 0301 basic medicine, Allergy, Veterinary medicine, Health, Toxicology and Mutagenesis, 030106 microbiology, [ SDV.BBM.BM ] Life Sciences [q-bio]/Biochemistry, Molecular Biology/Molecular biology, 010501 environmental sciences, Biology, Real-Time Polymerase Chain Reaction, 01 natural sciences, Risk Assessment, [ SDV.EE.SANT ] Life Sciences [q-bio]/Ecology, environment/Health, 03 medical and health sciences, Dogs, medicine, Animals, Humans, Screening tool, ComputingMilieux_MISCELLANEOUS, 0105 earth and related environmental sciences, [SDV.EE.SANT]Life Sciences [q-bio]/Ecology, environment/Health, CATS, Public Health, Environmental and Occupational Health, Dust, General Medicine, Environmental Exposure, Allergens, medicine.disease, Pollution, Large cohort, Air Pollution, Indoor, Cats, Cohort study
Abstract: Contradictory results are found in the literature concerning fungi, bacteria, and pet exposure and the risk of developing asthma. All these allergens have been thoroughly studied separately in cohort studies, and a variety of sampling and analytical methods are used. It is already possible to characterize fungi, mites, and bacteria by QPCR. The aim of our study is to evaluate QPCR systems to quantify the presence of cats and dogs in homes. Twenty-four houses were sampled with an Electrostatic Dust Collector which was analyzed by QPCR. Questionnaires on the presence of pets in homes were completed. The results from QPCR were correlated for real presence of cats and dogs, and highlighted indirect exposure. This study provides a useful screening tool that will be used in future large cohort studies, such as the ELFE cohort study.
Published: 2016

26. Compounds Triggering ER Stress Exert Anti-Melanoma Effects and Overcome BRAF Inhibitor Resistance

Author: Emilie Jaune, Hella Amdouni, Anne-Sophie Dabert-Gay, Jean-Sébastien Annicotte, Magali Plaisant, Solange Moréra, Delphine Debayle, Corine Bertolotto, Patricia Abbe, Thierry Passeron, Abdelali Lehraiki, Laurent Héliot, Robert Ballotti, Philippe Gual, Baharia Mograbi, Cyril Ronco, Mariano Gonzalez-Pisfil, Thomas Botton, Damien Alcor, Caroline Robert, Michael Cerezo, Stéphane Rocchi, Nabil Rabhi, Véronique Hofman, Armelle Vigouroux, Antoine Millet, Rachid Benhida, Maruf M.U. Ali, Paul Hofman, Florian Rouaud, Université Nice Sophia Antipolis - Faculté de Médecine (UNS UFR Médecine), Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA), Centre méditerranéen de médecine moléculaire (C3M), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institutions et Dynamiques Historiques de l'Économie et de la Société (IDHES), École normale supérieure - Cachan (ENS Cachan)-Université Panthéon-Sorbonne (UP1)-Université Paris 8 Vincennes-Saint-Denis (UP8)-Université Paris Nanterre (UPN)-Centre National de la Recherche Scientifique (CNRS)-Université d'Évry-Val-d'Essonne (UEVE), Institut de Chimie de Nice (ICN), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS), Service de Dermatologie [Nice], Hôpital Archet 2 [Nice] (CHU), Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Nice Sophia Antipolis (... - 2019) (UNS), Institut de pharmacologie moléculaire et cellulaire (IPMC), Centre d'Etudes Lasers Intenses et Applications (CELIA), Université de Bordeaux (UB)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS), Génomique Intégrative et Modélisation des Maladies Métaboliques (EGID), Université de Lille-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Centre National de la Recherche Scientifique (CNRS)-Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Laboratoire de Physique des Lasers, Atomes et Molécules - UMR 8523 (PhLAM), Université de Lille-Centre National de la Recherche Scientifique (CNRS), Institut Français de Recherche pour l'Exploitation de la Mer - Brest (IFREMER), Institut Français de Recherche pour l'Exploitation de la Mer (IFREMER), Microbiologie et enzymologie structurale (MESB3S), Département Biochimie, Biophysique et Biologie Structurale (B3S), Institut de Biologie Intégrative de la Cellule (I2BC), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Saclay-Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Saclay-Institut de Biologie Intégrative de la Cellule (I2BC), Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Saclay-Université Paris-Sud - Paris 11 (UP11)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Centre National de la Recherche Scientifique (CNRS)-Université Paris-Saclay, Laboratoire d'Enzymologie et Biochimie Structurales, Centre National de la Recherche Scientifique (CNRS), University of Stavanger, Laboratoire Chrono-environnement - UFC (UMR 6249) (LCE), Centre National de la Recherche Scientifique (CNRS)-Université de Franche-Comté (UFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Centre méditérannéen de médecine moléculaire ( C3M ), 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 ), Université Nice Sophia Antipolis - Faculté de Médecine ( UNS UFR Médecine ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ), Institut de Chimie de Nice ( ICN ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Centre National de la Recherche Scientifique ( CNRS ), Hôpital Archet 2 [Nice] ( CHU ), Institut de Recherche sur le Cancer et le Vieillissement ( IRCAN ), Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Institut National de la Santé et de la Recherche Médicale ( INSERM ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Pathologie Clinique et Expérimentale, Université Côte d'Azur ( UCA ) -Université Côte d'Azur ( UCA ) -Hôpital pasteur [Colmar]-CHU Nice, Institut de pharmacologie moléculaire et cellulaire ( IPMC ), Génomique Intégrative et Modélisation des Maladies Métaboliques ( EGID ), Institut Pasteur de Lille, Réseau International des Instituts Pasteur ( RIIP ) -Réseau International des Instituts Pasteur ( RIIP ) -Université de Lille-Centre Hospitalier Régional Universitaire [Lille] ( CHRU Lille ) -Centre National de la Recherche Scientifique ( CNRS ), Laboratoire de Physique des Lasers, Atomes et Molécules - UMR 8523 ( PhLAM ), Université de Lille-Centre National de la Recherche Scientifique ( CNRS ), Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy ( IGR ), Microbiologie et enzymologie structurale ( MESB3S ), Département Biochimie, Biophysique et Biologie Structurale ( B3S ), Institut de Biologie Intégrative de la Cellule ( I2BC ), Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Sud - Paris 11 ( UP11 ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Sud - Paris 11 ( UP11 ) -Institut de Biologie Intégrative de la Cellule ( I2BC ), Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Sud - Paris 11 ( UP11 ) -Université Paris-Saclay-Centre National de la Recherche Scientifique ( CNRS ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Université Paris-Sud - Paris 11 ( UP11 ), Department of Life Sciences, Imperial College London, Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), 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)-Université Côte d'Azur (UCA), Université Paris 1 Panthéon-Sorbonne (UP1)-Université Paris 8 Vincennes-Saint-Denis (UP8)-Université Paris Nanterre (UPN)-Université d'Évry-Val-d'Essonne (UEVE)-Centre National de la Recherche Scientifique (CNRS)-Ecole Normale Supérieure Paris-Saclay (ENS Paris Saclay), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), 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)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (EGENODIA (GI3M)), Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Institut de Biologie Intégrative de la Cellule (I2BC), Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université Paris-Saclay-Centre National de la Recherche Scientifique (CNRS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Hôpital pasteur [Colmar]-Centre Hospitalier Universitaire de Nice (CHU Nice), Institut Gustave Roussy (IGR), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA)-Université Nice Sophia Antipolis (... - 2019) (UNS), 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), Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 (GI3M), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Lille-Centre National de la Recherche Scientifique (CNRS)-Institut Pasteur de Lille, Réseau International des Instituts Pasteur (RIIP)-Réseau International des Instituts Pasteur (RIIP), Centre National de la Recherche Scientifique (CNRS)-Commissariat à l'énergie atomique et aux énergies alternatives (CEA)-Université de Bordeaux (UB), Institut Français de Recherche pour l'Exploitation de la Mer - Brest (IFREMER Centre de Bretagne), Institutions et Dynamiques Historiques de l'Économie et de la Société ( IDHES ), École normale supérieure - Cachan ( ENS Cachan ) -Université Panthéon-Sorbonne ( UP1 ) -Université Paris 8 Vincennes-Saint-Denis ( UP8 ) -Université Paris Nanterre ( UPN ) -Université d'Évry-Val-d'Essonne ( UEVE ) -Centre National de la Recherche Scientifique ( CNRS ), Centre d'Etudes Lasers Intenses et Applications ( CELIA ), Université de Bordeaux ( UB ) -Commissariat à l'énergie atomique et aux énergies alternatives ( CEA ) -Centre National de la Recherche Scientifique ( CNRS ), Institut Français de Recherche pour l'Exploitation de la Mer - Brest ( IFREMER ), Institut Français de Recherche pour l'Exploitation de la Mer ( IFREMER ), Centre National de la Recherche Scientifique ( CNRS ), Laboratoire Chrono-environnement ( LCE ), Université Bourgogne Franche-Comté ( UBFC ) -Centre National de la Recherche Scientifique ( CNRS ) -Université de Franche-Comté ( UFC ), and Houel, Ludivine
Subjects: 0301 basic medicine, Proto-Oncogene Proteins B-raf, Cancer Research, Programmed cell death, [SDV]Life Sciences [q-bio], Antineoplastic Agents, Pharmacology, Biology, Transcriptome, 03 medical and health sciences, Mice, 0302 clinical medicine, Cell Line, Tumor, medicine, Animals, Humans, Endoplasmic Reticulum Chaperone BiP, Melanoma, Protein Kinase Inhibitors, neoplasms, Heat-Shock Proteins, 030304 developmental biology, Cell Proliferation, Regulation of gene expression, 0303 health sciences, Sulfonamides, [ SDV ] Life Sciences [q-bio], Autophagy, Cell Biology, medicine.disease, Endoplasmic Reticulum Stress, Xenograft Model Antitumor Assays, [SDV] Life Sciences [q-bio], Gene Expression Regulation, Neoplastic, 030104 developmental biology, Oncology, Cell culture, Apoptosis, Drug Resistance, Neoplasm, 030220 oncology & carcinogenesis, Unfolded protein response, Cancer research
Abstract: International audience; Hepatitis B virus (HBV) is a small DNA virus that replicates by reverse transcription of a terminally redundant RNA, the pregenome. Specific packaging of this transcript into viral capsids is mediated by interaction of the reverse transcriptase, P protein, with the 5'-proximal encapsidation signal epsilon, epsilon-function is correlated with the formation of a hairpin structure containing a bulge and a loop, each consisting of 6 nt. To analyse the importance of primary sequence in these regions, we have combined selection of encapsidation competent individuals from pools of randomized epsilon-sequences in transfected cells with in vitro amplification, thus bypassing the current experimental limitations of the HBV system. While no alterations of the authentic loop sequence were detectable, many different sequences were tolerated in the 3'-part of the bulge. However, at the two 5'-proximal bulge positions the wt sequence was strongly selected for, indicating that for RNA packaging close contacts between protein and the 5'- but not the 3'-part of the bulge are important. Such a bipartite organisation provides a structural basis for the recently demonstrated special role of the 3'-part of the bulge as template for the first nucleotides of (-)-strand DNA in HBV reverse transcription.
Published: 2016

27. The scalp hair collar and tuft signs: A retrospective multicenter study of 78 patients with a systematic review of the literature

Author: C. Eschard, Jean-Philippe Lacour, Nausicaa Malissen, Juliette Mazereeuw-Hautier, Thomas Hubiche, Stéphanie Mallet, Emmanuel Mahé, Sébastien Barbarot, Valérie Rigau, Didier Bessis, Sylvie Fraitag, Ludovic Martin, Guillaume Captier, Nathalie Milla, C. Abasq, A. Phan, Marie-Christine Picot, Hassan El Fertit, Emmanuelle Bourrat, M. Marque, Christine Chiaverini, Olivia Boccara, Michèle Bigorre, Eve Puzenat, Nicolas Leboucq, Patrice Plantin, Pierre Vabres, F. Boralevi, Pathogénèse et contrôle des infections chroniques (PCCI), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Département de dermatologie [CHU de Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de chirurgie pédiatrique [Hôpital Lapeyronie-Arnaud de Villeneuve], Hôpital Lapeyronie [Montpellier] (CHU), Service de Dermatologie [Nice], Hôpital Archet 2 [Nice] (CHU), Service de dermatologie (Dermato - BREST), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Service de dermatologie [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Universitaire Carémeau [Nîmes] (CHU Nîmes), Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Département de Neuroradiologie[Montpellier], Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [CHU Montpellier], Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Université de Montpellier (UM), Service de dermatologie et pathologies vasculaires [CH Argenteuil], Centre Hospitalier Victor Dupouy, Service de dermatologie, vénéreologie et cancérologie cutanée [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Service de Dermatologie [CHU Angers] (PXE - le PseudoXanthome Elastique), Centre Hospitalier Universitaire d'Angers (CHU Angers), PRES Université Nantes Angers Le Mans (UNAM)-PRES Université Nantes Angers Le Mans (UNAM), Centre de référence des maladies rares de la peau et des muqueuses d’origine génétique [CHU Toulouse] (CRMRP), Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Service de Dermatologie, Centre Hospitalier Sud, Hospices Civils, Lyon, Service de dermatologie et vénérologie [Hôpital Laënnec, site de Quimper], CH Cornouaille, Département d'information médicale [Montpellier], Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon), Service de Dermatologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Biothérapies des maladies génétiques et cancers, Université Bordeaux Segalen - Bordeaux 2-Institut National de la Santé et de la Recherche Médicale (INSERM), Dermatologie pédiatrique - Bordeaux, CHU Bordeaux [Bordeaux], Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier )-Université de Montpellier (UM), Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Université Montpellier 1 (UM1)-Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Hôpital Gui de Chauliac [Montpellier]-Université de Montpellier (UM), Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), centre de référence des maladies rares de la peau, and CHU Toulouse [Toulouse]
Subjects: Male, Multimodal Imaging, MESH: Magnetic Resonance Imaging, 030207 dermatology & venereal diseases, paraganglioma, sebaceous nevus, 0302 clinical medicine, Meninges, Paraganglioma, MESH: Neuroimaging, Prospective Studies, meningocele, Ultrasonography, Doppler, Color, False Negative Reactions, MESH: False Negative Reactions, Neural Plate, cephalocele, medicine.diagnostic_test, hair tuft, membranous aplasia cutis, MESH: Infant, Newborn, MESH: Multimodal Imaging, Brain, MESH: Choristoma, MESH: Infant, Magnetic Resonance Imaging, 3. Good health, medicine.anatomical_structure, MESH: Skull, Female, Radiology, MESH: Hair, sinus pericranii, MESH: Tomography, X-Ray Computed, medicine.medical_specialty, MESH: Abnormalities, Multiple, MESH: Neural Plate, MESH: Meninges, Neuroimaging, Dermatology, MESH: Ultrasonography, Doppler, Color, Choristoma, MESH: Scalp, Veins, 03 medical and health sciences, MESH: Brain, medicine, Nevus, Humans, Abnormalities, Multiple, False Positive Reactions, Sinus pericranii, Retrospective Studies, Cephalocele, hair collar, MESH: Humans, Scalp, MESH: Veins, MESH: False Positive Reactions, business.industry, Skull, Infant, Newborn, Infant, Magnetic resonance imaging, MESH: Retrospective Studies, Neurovascular bundle, medicine.disease, MESH: Male, MESH: Prospective Studies, Surgery, smooth muscle cell nevus, business, Tomography, X-Ray Computed, MESH: Female, 030217 neurology & neurosurgery, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology, Hair
Abstract: International audience; BACKGROUND:Hair collar sign (HCS) and hair tuft of the scalp (HTS) are cutaneous signs of an underlying neuroectodermal defect, but most available data are based on case reports.OBJECTIVE:We sought to define the clinical spectrum of HCS and HTS, clarify the risk for underlying neurovascular anomalies, and provide imaging recommendations.METHODS:A 10-year multicenter retrospective and prospective analysis of clinical, radiologic, and histopathologic features of HCS and HTS in pediatric patients was performed.RESULTS:Of the 78 patients included in the study, 56 underwent cranial and brain imaging. Twenty-three of the 56 patients (41%) had abnormal findings, including the following: (1) cranial/bone defect (30.4%), with direct communication with the central nervous system in 28.6%; (2) venous malformations (25%); or (3) central nervous system abnormalities (12.5%). Meningeal heterotopia in 34.6% (9/26) was the most common neuroectodermal association. Sinus pericranii, paraganglioma, and combined nevus were also identified.LIMITATIONS:The partial retrospective design and predominant recruitment from the dermatology department are limitations of this study.CONCLUSIONS:Infants with HCS or HTS are at high risk for underlying neurovascular anomalies. Magnetic resonance imaging scans should be performed in order to refer the infant to the appropriate specialist for management.Copyright © 2016 American Academy of Dermatology, Inc. Published by Elsevier Inc. All rights reserved.
Published: 2016

28. Impact de l’âge et du sexe sur les aspects cliniques et épidémiologiques du psoriasis de l’enfant. Données d’une étude transversale multicentrique française

Author: Bonigen, J., Phan, A., Hadj-Rabia, S., Boralevi, F, Bursztejn, A.C., Bodemer, C., Ferneiny, M., Souillet, A.L., Chiaverini, C., Bourrat, E., Miquel, J., Vabres, P., Barbarot, S., Bessis, D., Eschard, C., Mazereeuw-Hautier, J., Piram, M., Plantin, P., Abasq, C., Lasek-Duriez, A., Maruani, A., Beauchet, A., Mahé, E., Société Française de Dermatologie Pédiatrique, Groupe de Recherche de la, Centre Hospitalier Victor Dupouy, Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL), Service de dermatologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5), Université Sorbonne Paris Cité (USPC), Hôpital Pellegrin, CHU Bordeaux [Bordeaux]-Groupe hospitalier Pellegrin, Service de Dermatologie et Allergologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de Dermatologie [Nice], Hôpital Archet 2 [Nice] (CHU), AP-HP Hôpital universitaire Robert-Debré [Paris], Service de Dermatologie [Rennes] = Dermatology [Rennes], CHU Pontchaillou [Rennes], CHR La réunion, Service de Dermatologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de dermatologie [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Pathogénèse et contrôle des infections chroniques (PCCI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Service de dermatologie (CHU de Reims), Centre Hospitalier Universitaire de Reims (CHU Reims), Service de dermatologie (CHU de Toulouse), CHU Toulouse [Toulouse], Service de Rhumatologie [CHU Bicêtre], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Bicêtre, Université Paris-Sud - Paris 11 (UP11), Centre hospitalier de Cornouaille, Service de dermatologie (Dermato - BREST), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Hôpital Saint-Vincent de Paul, Service de dermatologie (CHRU de Tours), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), Hôpital Ambroise Paré [AP-HP], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier d'Argenteuil, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Service de Dermatologie [Rennes], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Bicêtre, Hôpital Ambroise Paré, and Université de Versailles Saint-Quentin-en-Yvelines (UVSQ)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)
Subjects: Male, Enfant, Scalp, Nourrisson, Adolescent, Age Factors, Infant, Nail Diseases, Cross-Sectional Studies, Sex Factors, Child, Preschool, Humans, Psoriasis, Female, France, Child, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; BACKGROUNDThe prevalence of childhood psoriasis is estimated at between 0.4% and 0.7%. Clinical aspects of the diseases depend on age. The aim of this study was to investigate the clinical aspects of psoriasis according to age and sex.PATIENTS AND METHODSA cross-sectional, multicentre study of children with psoriasis was performed by investigators belonging to the Research Group of the French Society of Paediatric Dermatology. The study was conducted from April 2012 to March 2013. Inclusion criteria were age less than 18 years and clinical diagnosis of psoriasis. The children were classified into 3 groups by age: infants: 41%), but it accounted for only 25.9% of psoriasis of infants (P
Published: 2016

29. Systemic Treatments in Childhood Psoriasis: A French Multicentre Study on 154 Children

Author: Charbit, L., Mahé, E., Phan, A., Chiaverini, C., Boralevi, F., Bourrat, E., Lasek, A., Maruani, A., Aubin, F., Droitcourt, C., Barbarot, S., Mallet, S., Mazereeuw-Hautier, J., Begon, E., Abasq, C., Plantin, P., Souillet, A.-L., Hadj-Rabia, S., Bursztejn, A.-C., Dermatologie Pédiatrique, Groupe, Centre Hospitalier Victor Dupouy, Hôpital Femme Mère Enfant [CHU - HCL] (HFME), Hospices Civils de Lyon (HCL), Service de Dermatologie [Nice], Hôpital Archet 2 [Nice] (CHU), Service de dermatologie [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], CHU Bordeaux [Bordeaux], AP-HP Hôpital universitaire Robert-Debré [Paris], Groupe Hospitalier de l'Institut Catholique de Lille (GHICL), Université Francois Rabelais [Tours], Service de dermatologie, Unité de dermatologie pédiatrique, Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), MethodS in Patients-centered outcomes and HEalth ResEarch (SPHERE), Université de Tours-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Nantes - UFR des Sciences Pharmaceutiques et Biologiques, Université de Nantes (UN)-Université de Nantes (UN), Service de dermatologie (CHRU Besançon), Centre Hospitalier Régional Universitaire [Besançon] (CHRU Besançon), 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), CHU Pontchaillou [Rennes], Service de dermatologie [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Laboratoire de recherche en sciences de gestion Panthéon-Assas (LARGEPA), Université Panthéon-Assas (UP2), Service de dermatologie (CHU de Toulouse), CHU Toulouse [Toulouse], Centre Hospitalier René Dubos [Pontoise], Service de dermatologie (Dermato - BREST), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Centre hospitalier de Cornouaille, Service de dermatologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université Paris Descartes - Paris 5 (UPD5), Université Sorbonne Paris Cité (USPC), and Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy)
Subjects: medicine.medical_specialty, Adolescent, [SDV]Life Sciences [q-bio], Keratolytic, MEDLINE, Dermatology, Acitretin, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Childhood psoriasis, Keratolytic Agents, Psoriasis, medicine, Humans, Preschool, Child, ComputingMilieux_MISCELLANEOUS, business.industry, Phototherapy, medicine.disease, 3. Good health, Acitretina, Methotrexate, Treatment Outcome, Multicenter study, 030220 oncology & carcinogenesis, Child, Preschool, Cyclosporine, France, Dermatologic Agents, business, Immunosuppressive Agents, medicine.drug
Abstract: International audience
Published: 2016

30. ZEB1-mediated melanoma cell plasticity enhances resistance to MAPK inhibitors

Author: Stéphane Dalle, Corine Bertolotto, Emilie Thomas, Stéphane Ansieau, L. Depaepe, Marie‐Ambre Monet, Luc Thomas, Samia Mourah, Amélie Boespflug, Maud Ligier, Arnaud de la Fouchardière, Robert Ballotti, Alain Puisieux, Geoffrey Richard, Garance Tondeur, Maxime Battistella, Marie Perier-Muzet, Céleste Lebbé, Julie Caramel, Romain Barnault, Roxane M. Pommier, Pillet, Lauriane, Centre de Recherche en Cancérologie de Lyon (UNICANCER/CRCL), Centre Léon Bérard [Lyon]-Université Claude Bernard Lyon 1 (UCBL), Université de Lyon-Université de Lyon-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Service de Dermatologie [Nice], Hôpital Archet 2 [Nice] (CHU), Université Nice Sophia Antipolis - Faculté de Médecine (UNS UFR Médecine), Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Centre méditerranéen de médecine moléculaire (C3M), 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)-Université Côte d'Azur (UCA), 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), Service d'anatomo-pathologie [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Cancer et Transplantation : Physiopathologie et Réponse Thérapeutique (UMR 1165), Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Institut Universitaire d'Hématologie (IUH), Université Paris Diderot - Paris 7 (UPD7), Centre Hospitalier Lyon Sud [CHU - HCL] (CHLS), Hospices Civils de Lyon (HCL), Institut Universitaire de France (IUF), Ministère de l'Education nationale, de l’Enseignement supérieur et de la Recherche (M.E.N.E.S.R.), Université de Lyon-Université de Lyon-Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM), 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 National de la Santé et de la Recherche Médicale (INSERM), and Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)
Subjects: 0301 basic medicine, MAPK/ERK pathway, medicine.medical_treatment, Cellular differentiation, Biopsy, Cell Plasticity, Drug Resistance, Drug resistance, Growth, Targeted therapy, Melanoma, Research Articles, Cancer, Skin, Cell Death, Pigmentation, EMT, Cell Differentiation, targeted therapy, Adaptation, Physiological, 3. Good health, Phenotype, Molecular Medicine, Melanocytes, France, Research Article, Patients, Cells, Antineoplastic Agents, [SDV.CAN]Life Sciences [q-bio]/Cancer, Dermatology, Biology, Cell Line, resistance, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cell Line, Tumor, medicine, Humans, Protein Kinase Inhibitors, therapy, Carcinoma, Zinc Finger E-box-Binding Homeobox 1, medicine.disease, MAPK, 030104 developmental biology, Cell culture, Immunology, Cancer cell, Mutation, Cancer research, pathology, Laboratories
Abstract: International audience; Targeted therapies with MAPK inhibitors (MAPKi) are faced with severe problems of resistance in BRAF-mutant melanoma. In parallel to the acquisition of genetic mutations, melanoma cells may also adapt to the drugs through phenotype switching. The ZEB1 transcription factor, a known inducer of EMT and invasiveness, is now considered as a genuine oncogenic factor required for tumor initiation, cancer cell plasticity, and drug resistance in carcinomas. Here, we show that high levels of ZEB1 expression are associated with inherent resistance to MAPKi in BRAFV600-mutated cell lines and tumors. ZEB1 levels are also elevated in melanoma cells with acquired resistance and in biopsies from patients relapsing while under treatment. ZEB1 overexpression is sufficient to drive the emergence of resistance to MAPKi by promoting a reversible transition toward a MITFlow/p75high stem-like and tumorigenic phenotype. ZEB1 inhibition promotes cell differentiation, prevents tumorigenic growth in vivo, sensitizes naive melanoma cells to MAPKi, and induces cell death in resistant cells. Overall, our results demonstrate that ZEB1 is a major driver of melanoma cell plasticity, driving drug adaptation and phenotypic resistance to MAPKi
Published: 2016

31. Daylight photodynamic therapy with methyl aminolevulinate cream is effective and nearly painless in treating actinic keratoses: a randomised, investigator-blinded, controlled, phase III study throughout Europe

Author: Céline Girard, M. Tarstedt, V. von Felbert, Jean-Philippe Lacour, A. W. Venema, Pedro Redondo, B. Pérez-García, A. Tsianakas, Nabil Kerrouche, S. Leclerc, M. J. Gerritsen, Claas Ulrich, Henri Adamski, I. Synnerstad, C. Serra-Guillen, R.-M. Szeimies, Brigitte Dréno, Nicole W.J. Kelleners-Smeets, Nicole Basset-Seguin, Yolanda Gilaberte, Service de Dermatologie [Nice], Hôpital Archet 2 [Nice] (CHU), Hôpital Saint-Louis, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre hospitalier universitaire de Nantes (CHU Nantes), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Pathogénèse et contrôle des infections chroniques (PCCI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Service de Dermatologie [Rennes] = Dermatology [Rennes], CHU Pontchaillou [Rennes], GALDERMA R&D, Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Service de Dermatologie [Rennes], MUMC+: MA Dermatologie (9), Dermatologie, RS: GROW - Oncology, and RS: GROW - R3 - Innovative Cancer Diagnostics & Therapy
Subjects: Male, medicine.medical_specialty, Keratosis, Skin Cream, Pain, Dermatology, Severity of Illness Index, law.invention, Patient satisfaction, Randomized controlled trial, Methyl aminolevulinate, law, Severity of illness, medicine, Humans, Single-Blind Method, Adverse effect, Aged, Aged, 80 and over, Photosensitizing Agents, business.industry, Actinic keratosis, Aminolevulinic Acid, Middle Aged, medicine.disease, eye diseases, 3. Good health, Surgery, Europe, Keratosis, Actinic, Clinical trial, Treatment Outcome, Infectious Diseases, Photochemotherapy, Scalp Dermatoses, Patient Satisfaction, Sunlight, Female, business, Facial Dermatoses, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, medicine.drug
Abstract: International audience; BACKGROUND:Unmet needs exist in actinic keratosis (AK) treatment. Daylight photodynamic therapy (DL-PDT) has shown good efficacy and safety results compared to conventional PDT (c-PDT) in a recent Phase III multi-centre randomised controlled trial in Australia among 100 subjects with AKs.OBJECTIVES:Demonstrate non-inferior efficacy and superior safety of DL-PDT compared to c-PDT in treating multiple mild and/or moderate facial/scalp AKs.METHODS:Phase III, 12 week, multi-centre, randomised, investigator-blinded, controlled, intra-individual study conducted at different latitudes in Europe. AKs of adult subjects were treated once with methyl aminolevulinate (MAL) DL-PDT on one side of the face and MAL c-PDT contralaterally. Endpoints for DL-PDT concerned efficacy (non-inferiority regarding complete lesion response at week 12) and safety (superiority regarding subject's assessment of pain after treatment, on an 11-point numeric rating scale). Safety evaluation also included incidence of adverse events. Subject satisfaction was described using a questionnaire at baseline and last visit.RESULTS:At week 12, the total lesion complete response rate with DL-PDT was similar (non-inferior) to c-PDT (70% vs. 74%, respectively; 95% CI [-9.5; 2.4] in PP analysis, confirmed in ITT analysis). In addition, efficacy of DL-PDT was demonstrated regardless of weather conditions (sunny or cloudy). DL-PDT was nearly painless compared to c-PDT (0.7 vs. 4.4, respectively; P < 0.001), better tolerated and resulted in higher subject satisfaction.CONCLUSION:DL-PDT in comparison with c-PDT was as effective, better tolerated and nearly painless with high patient satisfaction, and may be considered a treatment of choice to meet needs of patients with mild or moderate facial/scalp AKs.
Published: 2015

32. Why and how immunohistochemistry should now be used to screen for the BRAFV600E status in metastatic melanoma? The experience of a single institution (LCEP, Nice, France)

Author: Kevin Washetine, Elodie Long, Marius Ilie, Sandra Lassalle, Paul Hofman, Philippe Bahadoran, Jérôme Mouroux, Pierre Laurent-Puig, Gilles Poissonnet, Virginie Lespinet, Véronique Hofman, Catherine Butori, Jean-Philippe Lacour, Valérie Taly, Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), 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)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Infection bactérienne, inflammation, et carcinogenèse digestive, COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-IFR50-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Centre de Lutte contre le Cancer Antoine Lacassagne [Nice] (UNICANCER/CAL), Université Côte d'Azur (UCA)-UNICANCER, Centre Hospitalier Universitaire de Nice (CHU Nice), Laboratoire de Pathologie Clinique et Expérimentale. Hôpital Pasteur [Nice], Hôpital Pasteur [Nice] (CHU), Service de Dermatologie [Nice], Hôpital Archet 2 [Nice] (CHU), Bases moléculaires de la réponse aux xénobiotiques (U775 (IFR95)), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre National de la Recherche Scientifique (CNRS), Médecine Personnalisée, Pharmacogénomique, Optimisation Thérapeutique (MEPPOT - U1147), Université Paris Descartes - Paris 5 (UPD5)-Institut National de la Santé et de la Recherche Médicale (INSERM), Laboratory of Clinical and Experimental Pathology, UNICANCER-Université Côte d'Azur (UCA), Centre Universitaires des Saints-Pères, Sorbonne Université (SU), Centre National de la Recherche Scientifique (CNRS)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Nice Sophia Antipolis (... - 2019) (UNS), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA), Université Côte d'Azur (UCA)-Université Côte d'Azur (UCA)-IFR50-Institut National de la Santé et de la Recherche Médicale (INSERM), CRLCC Antoine Lacassagne, TALY, Valerie, and Université Nice Sophia Antipolis (1965 - 2019) (UNS)
Subjects: Adult, Proto-Oncogene Proteins B-raf, Pathology, medicine.medical_specialty, Skin Neoplasms, Time Factors, Adolescent, Formalin fixed paraffin embedded, Metastatic melanoma, [SDV]Life Sciences [q-bio], Nice, Dermatology, Sensitivity and Specificity, Young Adult, Humans, Medicine, Single institution, Predictive testing, Melanoma, ComputingMilieux_MISCELLANEOUS, Aged, computer.programming_language, Aged, 80 and over, [SDV.MHEP] Life Sciences [q-bio]/Human health and pathology, business.industry, Sequence Analysis, DNA, Gold standard (test), Middle Aged, Immunohistochemistry, 3. Good health, Staining, [SDV] Life Sciences [q-bio], Infectious Diseases, Costs and Cost Analysis, Female, France, business, computer, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: Background Knowledge of the BRAFV600E status is mandatory in metastatic melanoma patients (MMP). Molecular biology is currently the gold standard method for status assessment. Objectives We assessed and compared the specificity, sensibility, cost-effectiveness and turnaround time (TAT) of immunohistochemistry (IHC) and molecular biology for detection of the BRAFV600E mutation in 188 MMP. Methods IHC, with the VE1 antibody, and pyrosequencing analysis were performed with formalin fixed paraffin embedded tumour samples. Results The BRAFV600E mutation was detected by pyrosequencing in 91/188 (48%) patients. IHC was strongly positive (3+) in all of these 91 cases. IHC was strongly positive in 9/188 (5%) cases in which the molecular testing failed due to non-amplifiable DNA. Weak or moderate staining was noted in 10/188 (5%) cases in which the molecular biology identified BRAF wild-type tumours. The ratio of the global cost for IHC/molecular biology testing was 1 : 2.2. The average TAT was 48 h vs. 96 h, for IHC vs. molecular biology testing, respectively. Conclusions This study showed that VE1 IHC should be a substitute for molecular biology in the initial assessment of the BRAFV600E status in MPP. This methodology needs to be set up in pathology laboratories in accordance with quality control/quality assurance accreditation procedures. Under these strict conditions the question is to know if BRAFV600E-IHC can serve not only as a prescreening tool, but also as a stand-alone test (at least in cases displaying an unequivocally staining pattern) as well as an alternative predictive test for samples for which the molecular biology failed.
Published: 2015

33. IGF1 Promotes Resistance to Apoptosis in Melanoma Cells through an Increased Expression of BCL2, BCL-X(L), and Survivin

Author: Sandy Giuliano, Lionel Larribère, Robert Ballotti, Caroline Hilmi, Karine Bille, Corine Bertolotto, Jean-Paul Ortonne, BERTOLOTTO-BALLOTTI, BERTOLOTTO-BALLOTTI, Biologie et pathologies des cellules mélanocytaires : de la pigmentation cutanée aux mélanomes, Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-IFR50-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Service de Dermatologie [Nice], Hôpital Archet 2 [Nice] (CHU), and Université Nice Sophia Antipolis (... - 2019) (UNS)
Subjects: Proto-Oncogene Proteins B-raf, endocrine system, Small interfering RNA, Survivin, bcl-X Protein, Apoptosis, [SDV.CAN]Life Sciences [q-bio]/Cancer, Dermatology, Biology, Inhibitor of apoptosis, Models, Biological, Biochemistry, Inhibitor of Apoptosis Proteins, TNF-Related Apoptosis-Inducing Ligand, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cell Line, Tumor, Humans, Gene silencing, Enzyme Inhibitors, Insulin-Like Growth Factor I, Phosphorylation, Melanoma, Molecular Biology, 030304 developmental biology, Regulation of gene expression, 0303 health sciences, Cell Biology, Staurosporine, Neoplasm Proteins, Cell biology, Gene Expression Regulation, Neoplastic, Proto-Oncogene Proteins c-bcl-2, UVB-induced apoptosis, 030220 oncology & carcinogenesis, Cancer research, Tumor necrosis factor alpha, Microtubule-Associated Proteins, hormones, hormone substitutes, and hormone antagonists
Abstract: International audience; IGF1 plays a key role in the development and growth of multiple tumors and in the prevention of apoptosis. In melanoma cells, IGF1 has been shown to mediate resistance to anoikis-induced apoptosis. However, the effect of IGF1 on other proapoptotic stimuli has never been reported. Further, the molecular mechanisms by which IGF1 mediates its prosurvival properties in melanoma cells remain unknown. Here, we demonstrate that IGF1 impairs the onset of tumor necrosis factor-related apoptosis-inducing ligand and staurosporine-induced apoptosis in melanoma cells expressing either wild-type or oncogenic B-Raf. Further, we show that IGF1 inhibits mitochondrial damage that occurs during apoptosis, thereby indicating that IGF1 acts at the level of mitochondria to mediate its antiapoptotic stimuli. Accordingly, IGF1 increases the mRNA levels and protein expression of antiapoptotic members of the BCL2 family--BCL2 and BCL-X(L)--and that of the inhibitor of apoptosis protein, survivin. Further, their specific silencing by small interfering RNA prevents the protective effect of IGF1. These findings therefore delineate the molecular mechanisms by which IGF1 mediates its prosurvival properties and provide a basis for clinical strategies designed to neutralize IGF1 or its target genes.
Published: 2008

34. Modalités pratiques de traitement des kératoses actiniques par photothérapie dynamique topique en lumière du jour avec l’aminolévulinate de méthyle

Author: Girard, Christian, Adamski, H., Basset-Séguin, N., Beaulieu, P., Dreno, B., Riboulet, J.-L., Lacour, J.-P., Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Pathogénèse et contrôle des infections chroniques (PCCI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Service de Dermatologie [Rennes] = Dermatology [Rennes], CHU Pontchaillou [Rennes], Service de Dermatologie [AP-HP Hôpital Saint-Louis], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Service de dermatologie [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), Service de Dermatologie [Nice], and Hôpital Archet 2 [Nice] (CHU)
Subjects: Lumière du jour, Photosensitizing Agents, Kératoses actiniques, Skin Cream, Pain, Aminolevulinic Acid, Photodynamic therapy, Aminolévulinate de méthyle, Keratosis, Actinic, Treatment Outcome, Clinical Protocols, Patient Education as Topic, Photochemotherapy, Scalp Dermatoses, Sunlight, Daylight, Humans, Actinic keratosis, Methyl aminolevulinate, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology, Facial Dermatoses, Photothérapie dynamique topique
Abstract: International audience; Actinic keratosis (AK), also known as solar keratosis or pre-cancerous keratosis, is frequently observed in areas of skin exposed to sunlight, particularly in light-skinned patients. In France, photodynamic therapy using red light (conventional PDT) and methylamino 5-levulinate (MAL) is indicated in the treatment of thin or non-hyperkeratotic and non-pigmented multiple AK lesions or large zones covered with AK lesions. It is well-known for its efficacy but also for its side effects, especially pain during illumination, which can limit its use. An alternative to PDT using natural daylight has recently been proposed to treat actinic keratosis lesions, and results in greater flexibility as well as significant reduction in pain. The lesions are prepared as for conventional PDT, with MAL cream being applied by the physician or the patient, after which they are exposed to natural daylight for 2hours. The lesions are then gently cleansed and protected from natural light for 24hours. This paper seeks to provide a precise description of the daylight PDT procedure for the treatment of AK.
Published: 2015

35. Pigmented macules of bony prominences (PMBP): A distinct presentation in patients with red hair

Author: Jean-Philippe Lacour, Annabel Maruani, Stéphanie Mallet, J. Miquel, Didier Bessis, Thomas Hubiche, C. Abasq, Christine Chiaverini, Nathalie Cardot-Leccia, Emilie Marmottant, Thierry Passeron, Service de Dermatologie [Nice], Hôpital Archet 2 [Nice] (CHU), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Pathogénèse et contrôle des infections chroniques (PCCI), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM), Centre Hospitalier Intercommunal Fréjus - St Raphaël (CHI Fréjus - St Raphaël), Service de dermatologie, vénéreologie et cancérologie cutanée [Hôpital de la Timone - APHM], Aix Marseille Université (AMU)-Assistance Publique - Hôpitaux de Marseille (APHM)- Hôpital de la Timone [CHU - APHM] (TIMONE), Service de dermatologie (CHRU de Tours), Service de dermatologie (Dermato - BREST), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), CHU Sud Saint Pierre [Ile de la Réunion], Centre Hospitalier Universitaire de Nice (CHU Nice), Centre méditerranéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (1965 - 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)-Université Côte d'Azur (UCA), Institut National de la Santé et de la Recherche Médicale (INSERM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier )-Université de Montpellier (UM), Hôpital de la Timone [CHU - APHM] (TIMONE)-Assistance Publique - Hôpitaux de Marseille (APHM)-Aix Marseille Université (AMU), Centre Hospitalier Régional Universitaire de Tours (CHRU TOURS), 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 National de la Santé et de la Recherche Médicale (INSERM), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), and Centre Hospitalier Régional Universitaire de Tours (CHRU Tours)
Subjects: Male, Pathology, medicine.medical_specialty, Adolescent, Skin Pigmentation, Dermatology, Solar prominence, 030207 dermatology & venereal diseases, 03 medical and health sciences, Young Adult, 0302 clinical medicine, Hyperpigmentation, Elbow, Medicine, Humans, In patient, Knee, 10. No inequality, Hair Color, ComputingMilieux_MISCELLANEOUS, business.industry, Hand, 030220 oncology & carcinogenesis, Female, Presentation (obstetrics), business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience
Published: 2015

36. [Wells Syndrome in children and atopy: Retrospective study of 11 cases and review of the literature]

Author: Brun, J., Chiaverini, C., Bessis, D., Bourrat, E., Lasek-Duriez, A., Hadj-Rabia, S., Boralevi, F., Lacour, J-P, Société Française de Dermatologie Pédiatrique, Groupe de Recherche de la, Service de Dermatologie [Nice], Hôpital Archet 2 [Nice] (CHU), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Pathogénèse et contrôle des infections chroniques (PCCI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), AP-HP Hôpital universitaire Robert-Debré [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Centre Hospitalier Régional Universitaire [Lille] (CHRU Lille), Service de dermatologie [CHU Necker], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-CHU Necker - Enfants Malades [AP-HP], CHU Necker - Enfants Malades [AP-HP], Service de dermatologie [Bordeaux], Université Bordeaux Segalen - Bordeaux 2-CHU Bordeaux [Bordeaux]-Hôpital Haut-Lévêque [CHU Bordeaux], and CHU Bordeaux [Bordeaux]
Subjects: Male, Atopie, Enfant, Urticaria, Neutrophils, Eczema, Wells’ syndrome, Dermatitis, Atopic, Eosinophilia, Humans, Corticothérapie, Child, Retrospective Studies, Atopy, Pruritus, Cellulitis, Syndrome de Wells, Dermis, Asthma, Child, Preschool, Infiltrat éosinophilique, Female, Steroids, Eosinophilic infiltrate, Food Hypersensitivity, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience; BACKGROUND:Well's syndrome, or eosinophilic cellulitis, is rare in childhood, with fewer than 40 pediatric cases being reported since 1979. The physiopathology is unknown.PATIENTS AND METHODS:In February 2012, members of the research group of the Department of Pediatric Dermatology Society submitted their case of Wells' syndrome in children aged 0-15 years. Details of clinical, biological and histological features and of therapeutic strategies were collected by physicians using a standardized questionnaire. Pictures were reviewed by the authors.RESULTS:Eleven patients were included (average age: 6 years), with a strong prevalence of atopy (63%). Two types of clinical manifestation were noted: single or multiple cellulitis associated or not with vesiculobullous lesions and fixed urticaria. Eighty-two percent of patients had pruritus and 73% had eosinophilia. For all patients, histological examination of skin biopsies showed an eosinophilic infiltrate extending in the dermis with associated Sweet-like neutrophilic infiltrate being seen in 2 patients. The course of the disease was protracted (mean duration: 8 months) with flare-ups. Treatment varied depending on the doctors (topical or systemic steroids, tacrolimus and dapsone).DISCUSSION:Our study confirms some of the data in the literature concerning the clinical, histological features and course of Well's syndrome in children. The key information is the high prevalence of atopic children hitherto unreported. In a setting of insect bites, vaccination, infection or traumatism, this unusual background could explain the onset of inflammatory reaction with eosinophils. Oral or topical steroids appear to be the first-line treatment in children when necessary.CONCLUSION:Well's syndrome in children is rare and characterized by its polymorphism. We report for the first time in a series of patients a high prevalence of atopy, which raises new perspectives in understanding these rare diseases. We propose topical steroids as first-line therapy in children with superficial lesions, with oral steroids being given for cellulitic lesions or where topical therapy fails.
Published: 2015

37. Oral erythromycin therapy in epidermolysis bullosa simplex generalized severe

Author: Jean-Philippe Lacour, Pierre Vabres, Guerrino Meneguzzi, A. Charlesworth, Christine Chiaverini, J. Mazereeuw, Didier Bessis, E. Fontas, Service de Dermatologie [Nice], Hôpital Archet 2 [Nice] (CHU), Institut de Recherche sur le Cancer et le Vieillissement (IRCAN), 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)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Centre Hospitalier Universitaire de Nice (CHU Nice), Service de Dermatologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Pathogénèse et contrôle des infections chroniques (PCCI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), Service de dermatologie (CHU de Toulouse), and CHU Toulouse [Toulouse]
Subjects: Male, medicine.medical_specialty, Staphylococcus aureus, Treatment outcome, Administration, Oral, Dermatology, medicine.disease_cause, Clinical study, Epidermolysis bullosa simplex, Streptococcal Infections, medicine, Humans, Oral erythromycin, Child, ComputingMilieux_MISCELLANEOUS, Streptococcus, business.industry, Infant, Skin Diseases, Bacterial, medicine.disease, Anti-Bacterial Agents, Erythromycin, Treatment Outcome, Child, Preschool, Epidermolysis Bullosa Simplex, Female, Staphylococcal Skin Infections, Dermatologic Agents, business, [SDV.MHEP]Life Sciences [q-bio]/Human health and pathology
Abstract: International audience
Published: 2015

38. Factors Associated with Impaired Quality of Life in Adult Patients Suffering from Ichthyosis

Author: Emmanuelle Bourrat, Isabelle Dreyfus, Annabel Maruani, Juliette Mazereeuw-Hautier, Didier Bessis, Pierre Vabres, Khaled Ezzedine, Christine Chiaverini, Hôpital Larrey [Toulouse], CHU Toulouse [Toulouse], Hopital Saint-Louis [AP-HP] (AP-HP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), CHU Trousseau [Tours], Centre Hospitalier Régional Universitaire de Tours (CHRU Tours), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Service de Dermatologie [Nice], Hôpital Archet 2 [Nice] (CHU), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), and CHU Bordeaux [Bordeaux]
Subjects: Male, Pediatrics, MESH: Ichthyosis / diagnosis, MESH: Cost of Illness, Severity of Illness Index, MESH: Pain / psychology, MESH: Ichthyosis / psychology, MESH: Ichthyosis / therapy, 030207 dermatology & venereal diseases, 0302 clinical medicine, MESH: Aged, 80 and over, MESH: Quality of Life, Cost of Illness, Risk Factors, MESH: Risk Factors, [SDV.MHEP.MI]Life Sciences [q-bio]/Human health and pathology/Infectious diseases, Surveys and Questionnaires, MESH: Child, Activities of Daily Living, Medicine, MESH: Pain / diagnosis, Prospective Studies, Child, Aged, 80 and over, MESH: Aged, MESH: Middle Aged, Ichthyosis, General Medicine, Middle Aged, MESH: Interpersonal Relations, MESH: Infant, humanities, 3. Good health, MESH: Young Adult, 030220 oncology & carcinogenesis, Child, Preschool, Female, France, Adult, medicine.medical_specialty, Adolescent, Pain, Dermatology, 03 medical and health sciences, Young Adult, Quality of life (healthcare), Sex Factors, MESH: Sex Factors, MESH: Severity of Illness Index, Humans, Interpersonal Relations, MESH: Surveys and Questionnaires, Psychiatry, Aged, MESH: Adolescent, MESH: Humans, Adult patients, business.industry, MESH: Activities of Daily Living, MESH: Child, Preschool, Infant, MESH: Adult, medicine.disease, MESH: Male, MESH: Prospective Studies, MESH: France, Quality of Life, business, MESH: Female
Abstract: International audience; Inherited ichthyoses are genetic disorders of cornification characterised by scaling of various aspects and severity, often associated with erythroderma. The skin is usually uncomfortable, pruriginous and painful and no specific treatment is available. Impact on quality of life (QoL) was previously demonstrated. QoL is a dynamic process that can be defined as an individual perception of one’s position in life. In order to improve patient’s management, the aim of our study was to determine the impact of weighted factors associated with impaired QoL in adult ichthyosis patients.
Published: 2014

39. Sentinel Node Status and Immunosuppression: Recurrence Factors in Localized Merkel Cell Carcinoma

Author: P.-E. Stoebner, Emeline Kubica, Christophe Bedane, Catherine Lok, Anne-Bénédicte Duval-Modeste, Thomas Jouary, Christina Mateus, Sandrine Mansard, Khaled Ezzedine, Florence Granel-Brocard, Marie-Thérèse Leccia, Anne Dompmartin, Jean-Philippe Lacour, Bernard Guillot, Philippe Saiag, Stéphane Dalle, Abou Diallo, Cécile Pagès, François Aubin, Sophie Dalac, Herrada, Anthony, Service de dermatologie Hôpital Saint-André Bordeaux, CHU Bordeaux [Bordeaux], Centre Léon Bérard [Lyon], Hôpital Saint-Louis, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7), Service de Dermatologie [Rouen], Hôpital Charles Nicolle [Rouen], CHU Rouen, Normandie Université (NU)-Normandie Université (NU)-CHU Rouen, Normandie Université (NU)-Normandie Université (NU), Centre Hospitalier Régional Universitaire [Montpellier] (CHRU Montpellier), Pathogénèse et contrôle des infections chroniques (PCCI), Institut National de la Santé et de la Recherche Médicale (INSERM)-Université de Montpellier (UM)-Centre Hospitalier Universitaire de Montpellier (CHU Montpellier ), CHU Clermont-Ferrand, Hôpital Ambroise Paré [AP-HP], Département de dermatologie, Centre Hospitalier Régional Universitaire de Besançon (CHRU Besançon)-Hôpital Saint-Jacques-Université de Franche-Comté (UFC), Université Bourgogne Franche-Comté [COMUE] (UBFC)-Université Bourgogne Franche-Comté [COMUE] (UBFC), Service de Dermatologie [CHU Limoges], CHU Limoges, Service de Dermatologie (CHU de Dijon), Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Service de Dermatologie [CHU Caen], Université de Caen Normandie (UNICAEN), Normandie Université (NU)-Normandie Université (NU)-CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Tumorothèque de Caen Basse-Normandie (TCBN), Service de Dermatologie et Allergologie [CHRU Nancy], Centre Hospitalier Régional Universitaire de Nancy (CHRU Nancy), Service de dermatologie [CHU d'Amiens-Picardie], CHU Amiens-Picardie, Centre Hospitalier Universitaire de Nîmes (CHU Nîmes), Institut des Biomolécules Max Mousseron [Pôle Chimie Balard] (IBMM), Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Centre National de la Recherche Scientifique (CNRS), Service de Dermatologie [Nice], Hôpital Archet 2 [Nice] (CHU), CHU Grenoble, Institut de Santé Publique, d'Epidémiologie et de Développement (ISPED), Université Bordeaux Segalen - Bordeaux 2, Oncologie dermatologique, Département de médecine oncologique [Gustave Roussy], Institut Gustave Roussy (IGR)-Institut Gustave Roussy (IGR), Université Paris Diderot - Paris 7 (UPD7)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Hôpital Charles Nicolle [Rouen]-CHU Rouen, CHU Caen, Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Normandie Université (NU)-Tumorothèque de Caen Basse-Normandie (TCBN)-Université de Caen Normandie (UNICAEN), Normandie Université (NU), and Centre National de la Recherche Scientifique (CNRS)-Institut de Chimie du CNRS (INC)-Université de Montpellier (UM)-Ecole Nationale Supérieure de Chimie de Montpellier (ENSCM)
Subjects: Male, Oncology, Pathology, Skin Neoplasms, Time Factors, medicine.medical_treatment, Kaplan-Meier Estimate, 030207 dermatology & venereal diseases, Merkel cell carcinoma, 0302 clinical medicine, Risk Factors, Medicine, Aged, 80 and over, education.field_of_study, medicine.diagnostic_test, Immunosuppression, General Medicine, Middle Aged, Sentinel node, 3. Good health, Treatment Outcome, Lymphatic Metastasis, 030220 oncology & carcinogenesis, Female, France, Adult, medicine.medical_specialty, Population, Sentinel lymph node, Dermatology, Risk Assessment, Disease-Free Survival, Immunocompromised Host, Young Adult, 03 medical and health sciences, Sex Factors, Predictive Value of Tests, Internal medicine, Biopsy, Humans, education, radiotherapy, Aged, Neoplasm Staging, Proportional Hazards Models, Retrospective Studies, Chi-Square Distribution, Sentinel Lymph Node Biopsy, business.industry, Retrospective cohort study, [SDV.MHEP.DERM] Life Sciences [q-bio]/Human health and pathology/Dermatology, medicine.disease, Carcinoma, Merkel Cell, Radiation therapy, Logistic Models, sentinel node, Multivariate Analysis, Feasibility Studies, Lymph Nodes, Neoplasm Recurrence, Local, business, prognostic, [SDV.MHEP.DERM]Life Sciences [q-bio]/Human health and pathology/Dermatology
Abstract: International audience; The prognostic value of the sentinel lymph node in Merkel cell carcinoma (MCC) has been examined previously in heterogeneous retrospective studies. The current retrospective study included a homogeneous population of patients with a localized MCC, all staged with sentinel lymph node biopsy. Factors associated with 3-year progression-free survival were analysed using logistic regression. The sentinel lymph node was positive in 32% of patients. The recurrence rate was 26.9%. In first analyses (n = 108), gender (p = 0.0115) and the presence of immunosuppression (p = 0.0494) were the only significant independent factors. In further analyses (n = 80), excluding patients treated with regional radiotherapy, sentinel lymph node status was the only significant prognostic factor (p = 0.0281). Immunosuppression and positive sentinel lymph node are associated with a worse prognosis in patients with MCC. Nodal irradiation impacts on the prognostic value of the sentinel lymph node status.
Published: 2014

40. A randomized investigator-masked double-bind placebo-controlled trial on thalidomide in severe cutaneous sarcoidosis

Author: Jacqueline Chevrant-Breton, Caroline Juillard, Michel Rybojad, Nicolas Dupin, Raphaël Porcher, Michel d’Incan, Jean Revuz, Anne Cosnes, Laurent Misery, Abdellatif Tazi, Catherine Droitcourt, Jean-Philippe Lacour, Alain Dupuy, Kristell Desseaux, Bénédicte Lebrun-Vignes, Pascal Joly, Dominique Valeyre, Bruno Sassolas, Olivier Chosidow, 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), Service de Dermatologie [Rennes] = Dermatology [Rennes], CHU Pontchaillou [Rennes], Modèles, Dynamiques, Corpus (MoDyCo), Université Paris Nanterre (UPN)-Centre National de la Recherche Scientifique (CNRS), Biostatistique et épidemiologie clinique, Université Paris Diderot - Paris 7 (UPD7)-Institut National de la Santé et de la Recherche Médicale (INSERM), Service de Dermatologie, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Henri Mondor, Laboratoire Jacques-Louis Lions (LJLL), Université Pierre et Marie Curie - Paris 6 (UPMC)-Université Paris Diderot - Paris 7 (UPD7)-Centre National de la Recherche Scientifique (CNRS), Service de Dermatologie [Nice], Hôpital Archet 2 [Nice] (CHU), Hôtel-Dieu, Hôpital Cochin [AP-HP], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Département de Médecine Interne et Pneumologie [Brest] (DMIP - Brest), Centre Hospitalier Régional Universitaire de Brest (CHRU Brest), Groupe d'Etude de la Thrombose de Bretagne Occidentale (GETBO), Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO)-Université de Brest (UBO), Service de dermatologie, Laboratoire de Neurosciences de Brest (LNB), Université de Brest (UBO), Centre Régional de Pharmacovigilance (CRPV), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Service d'informatique médicale, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Service des maladies respiratoires, Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Groupe Hospitalier Avicenne-Jean Verdier-René Muret, Service de dermatologie [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 pneumologie [Saint-Louis], Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP)-Assistance publique - Hôpitaux de Paris (AP-HP) (AP-HP), Université de Rennes (UR)-Hôpital Pontchaillou-Institut National de la Santé et de la Recherche Médicale (INSERM), Université de Brest (UBO)-Institut National de la Santé et de la Recherche Médicale (INSERM)-Institut Brestois Santé Agro Matière (IBSAM), Université de Brest (UBO)-Université de Brest (UBO), Service de Dermatologie [Rennes], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri-Mondor, CHU Cochin [AP-HP], Université de Brest (UBO)-Institut Brestois Santé Agro Matière (IBSAM), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Européen Georges Pompidou [APHP] (HEGP), Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpitaux Universitaires Paris Ouest - Hôpitaux Universitaires Île de France Ouest (HUPO), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Université Paris Diderot - Paris 7 (UPD7)-Groupe Hospitalier Saint Louis - Lariboisière - Fernand Widal [Paris], Assistance publique - Hôpitaux de Paris (AP-HP) (APHP), Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Groupe Hospitalier Avicenne-Jean Verdier-René Muret, Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Hôpital Henri Mondor-Université Paris-Est Créteil Val-de-Marne - Paris 12 (UPEC UP12), and Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)-Assistance publique - Hôpitaux de Paris (AP-HP) (APHP)
Subjects: Adult, Male, Pulmonary and Respiratory Medicine, medicine.medical_specialty, Sarcoidosis, Cutaneous Sarcoidosis, Population, Placebo-controlled study, Context (language use), Critical Care and Intensive Care Medicine, Placebo, Skin Diseases, law.invention, Young Adult, 030207 dermatology & venereal diseases, 03 medical and health sciences, 0302 clinical medicine, Double-Blind Method, Randomized controlled trial, law, Internal medicine, medicine, Humans, education, Aged, education.field_of_study, [SDV.GEN]Life Sciences [q-bio]/Genetics, Intention-to-treat analysis, business.industry, Remission Induction, Middle Aged, Thalidomide, 3. Good health, Surgery, Treatment Outcome, 030228 respiratory system, Female, France, Cardiology and Cardiovascular Medicine, business, Immunosuppressive Agents, medicine.drug
Abstract: International audience; Abstract: Context:Thalidomide use in cutaneous sarcoidosis is based on data from small case series or case reports. Objective:To evaluate the efficacy and safety of thalidomide in severe cutaneous sarcoidosis. Design, Setting and Participants:Randomized, double-bind, parallel, placebo-controlled, investigator-masked, multicentre trial lasting 3 months, and an open-label study from month 3 to month 6. Adults with clinical and histological diagnosis of cutaneous sarcoidosis were included in nine hospital centres in France. Intervention:Patients were randomized 1:1 to oral thalidomide (100 mg once daily) or to a matching oral placebo for three months. In the course of an open-label follow-up from month 3 to month 6, all patients received thalidomide 100 mg to 200 mg daily. Main outcome measures:The proportions of patients with a partial or complete cutaneous response at month 3, based on at least a 50% improvement of 3 target lesions scored for area and infiltration, were compared across randomisation groups. Results:The intent-to-treat population included 39 patients. None of them had a complete cutaneous response. Four out of 20 patients (20%) in the thalidomide group vs 4 out of 19 patients in the placebo group (21%) had a partial cutaneous response at month 3 (difference in proportion of -1% (95% CI -26% to +24%) for thalidomide vs placebo; p=1.0). Eight patients with side effects were recorded in the thalidomide group vs 3 in the placebo group. We observed a large number of adverse event-related discontinuations in patients under thalidomide in the first 3 months (4 patients with thalidomide, 0 with placebo), and in the 3 following months (5 patients). Conclusion:At a dose of 100 mg daily for 3 months, our results do not encourage thalidomide use in cutaneous sarcoidosis. Trial registration:NCT0030552 (ClinicalTrial.gov). Context: Thalidomide use in cutaneous sarcoidosis is based on data from small case series or case reports. Objective: To evaluate the efficacy and safety of thalidomide in severe cutaneous sarcoidosis. Design, Setting and Participants: Randomized, double-bind, parallel, placebo-controlled, investigator-masked, multicentre trial lasting 3 months, and an open-label study from month 3 to month 6. Adults with clinical and histological diagnosis of cutaneous sarcoidosis were included in nine hospital centres in France. Intervention: Patients were randomized 1:1 to oral thalidomide (100 mg once daily) or to a matching oral placebo for three months. In the course of an open-label follow-up from month 3 to month 6, all patients received thalidomide 100 mg to 200 mg daily. Main outcome measures: The proportions of patients with a partial or complete cutaneous response at month 3, based on at least a 50% improvement of 3 target lesions scored for area and infiltration, were compared across randomisation groups. Results: The intent-to-treat population included 39 patients. None of them had a complete cutaneous response. Four out of 20 patients (20%) in the thalidomide group vs 4 out of 19 patients in the placebo group (21%) had a partial cutaneous response at month 3 (difference in proportion of -1% (95% CI -26% to +24%) for thalidomide vs placebo; p=1.0). Eight patients with side effects were recorded in the thalidomide group vs 3 in the placebo group. We observed a large number of adverse event-related discontinuations in patients under thalidomide in the first 3 months (4 patients with thalidomide, 0 with placebo), and in the 3 following months (5 patients). Conclusion: At a dose of 100 mg daily for 3 months, our results do not encourage thalidomide use in cutaneous sarcoidosis. Trial registration: NCT0030552 (ClinicalTrial.gov).
Published: 2014

41. Secretome from senescent melanoma engages the STAT3 pathway to favor reprogramming of naive melanoma towards a tumor-initiating cell phenotype

Author: Jean-Philippe Lacour, Robert Ballotti, Damien Giacchero, Mickaël Ohanna, Caroline Bonet, Glen M. Boyle, Sandy Giuliano, Nicholas F Hayward, Philippe Bahadoran, Marylin Allegra, Vanessa F. Bonazzi, Yann Cheli, Corine Bertolotto, Karine Bille, Centre méditerranéen de médecine moléculaire (C3M), 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 National de la Santé et de la Recherche Médicale (INSERM), Queensland Institute of Medical Research, Service de Dermatologie [Nice], Hôpital Archet 2 [Nice] (CHU), BERTOLOTTO-BALLOTTI, BERTOLOTTO-BALLOTTI, Université Nice Sophia Antipolis (1965 - 2019) (UNS), and 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)-Université Côte d'Azur (UCA)
Subjects: Homeobox protein NANOG, STAT3 Transcription Factor, senescence, Cell, Population, Mice, Nude, [SDV.CAN]Life Sciences [q-bio]/Cancer, Cell Growth Processes, Biology, Transfection, STAT3, 03 medical and health sciences, Mice, Random Allocation, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cell Line, Tumor, medicine, melanoma, Animals, Humans, RNA, Small Interfering, education, neoplasms, Cellular Senescence, 030304 developmental biology, 0303 health sciences, education.field_of_study, Melanoma, medicine.disease, Phenotype, Xenograft Model Antitumor Assays, Gene Expression Regulation, Neoplastic, secretome, medicine.anatomical_structure, Oncology, 030220 oncology & carcinogenesis, Cancer research, Neoplastic Stem Cells, Female, Cell aging, Reprogramming, Research Paper, Signal Transduction
Abstract: // Mickael Ohanna 1,2,* , Yann Cheli 1,2,* , Caroline Bonet 1,2 , Vanessa F Bonazzi 4 , Marylin Allegra 1,3 , Sandy Giuliano 1,2 , Karine Bille 1,2 , Philippe Bahadoran 1,2,3 , Damien Giacchero 3 , Jean Philippe Lacour 2,3 , Glen M Boyle 4 , Nicholas F Hayward 4 , Corine Bertolotto 1,2,* and Robert Ballotti 1,2,3,* . 1 Inserm U1065, Centre Mediterraneen de Medecine Moleculaire, Equipe 1, Biologie et pathologies des melanocytes: de la pigmentation cutanee au melanome. Equipe labellisee Ligue 2013, Nice, F-06204, France 2 Universite de Nice Sophia-Antipolis, UFR Medecine, Nice, F-06107, France 3 Centre Hospitalier Universitaire, Service de Dermatologie, Nice, F-06204, France 4 Queensland Institute of Medical Research, 300 Herston Road, Herston, Brisbane 4006, Australia * These authors equally contributed to the work Correspondence: Robert Ballotti, email: // Keywords : melanoma, senescence, secretome, STAT3 Received : June 30, 2013 Accepted : August 17, 2013 Published : August 19, 2013 Abstract Here, we showed that the secretome of senescent melanoma cells drives basal melanoma cells towards a mesenchymal phenotype, with characteristic of stems illustrated by increased level of the prototype genes FN1, SNAIL, OCT4 and NANOG. This molecular reprogramming leads to an increase in the low-MITF and slow-growing cell population endowed with melanoma-initiating cell features. The secretome of senescent melanoma cells induces a panel of 52 genes, involved in cell movement and cell/cell interaction, among which AXL and ALDH1A3 have been implicated in melanoma development. We found that the secretome of senescent melanoma cells activates the STAT3 pathway and STAT3 inhibition prevents secretome effects, including the acquisition of tumorigenic properties. Collectively, the findings provide insights into how the secretome of melanoma cells entering senescence upon chemotherapy treatments increases the tumorigenicity of naive melanoma cells by inducing, through STAT3 activation, a melanoma-initiating cell phenotype that could favor chemotherapy resistance and relapse.
Published: 2013

42. Ichtyoses héréditaires : étude épidémiologique sur le territoire français

Author: Juliette Mazereeuw-Hautier, Isabelle Dreyfus, Stéphanie Mallet, J. Dupuis, Pierre Vabres, Sébastien Barbarot, C. Chouquet, Ludovic Martin, Khaled Ezzedine, Christine Chiaverini, Institut de Mathématiques de Toulouse UMR5219 (IMT), Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Institut National des Sciences Appliquées (INSA)-Université Toulouse 1 Capitole (UT1), Université Fédérale Toulouse Midi-Pyrénées-Université Fédérale Toulouse Midi-Pyrénées-Université Toulouse - Jean Jaurès (UT2J)-Université Toulouse III - Paul Sabatier (UT3), Université Fédérale Toulouse Midi-Pyrénées-Centre National de la Recherche Scientifique (CNRS), Service de dermatologie Hôpital Saint-André Bordeaux, CHU Bordeaux [Bordeaux], Service de Dermatologie [Nice], Hôpital Archet 2 [Nice] (CHU), Lipides - Nutrition - Cancer [Dijon - U1231] (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, Service de Pathologie [CHU de Dijon], Centre Hospitalier Universitaire de Dijon - Hôpital François Mitterrand (CHU Dijon), Laboratoire de recherche en sciences de gestion Panthéon-Assas (LARGEPA), Université Panthéon-Assas (UP2), Service de dermatologie [Nantes], Université de Nantes (UN)-Centre hospitalier universitaire de Nantes (CHU Nantes), UMR CNRS 8179, Université de Lille, Sciences et Technologies-Centre National de la Recherche Scientifique (CNRS), Service de dermatologie (CHU de Toulouse), CHU Toulouse [Toulouse], Université Toulouse Capitole (UT Capitole), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National des Sciences Appliquées - Toulouse (INSA Toulouse), Institut National des Sciences Appliquées (INSA)-Université de Toulouse (UT)-Institut National des Sciences Appliquées (INSA)-Université Toulouse - Jean Jaurès (UT2J), Université de Toulouse (UT)-Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Centre National de la Recherche Scientifique (CNRS), Service Dermatologie [CHU Toulouse], Pôle Clinique des Voies respiratoires [CHU Toulouse], Centre Hospitalier Universitaire de Toulouse (CHU Toulouse)-Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Chouquet, Cécile, Centre Hospitalier Universitaire de Toulouse (CHU Toulouse), Unité différenciation épidermique et auto-immunité rhumatoïde (UDEAR), Université Toulouse III - Paul Sabatier (UT3), Université de Toulouse (UT)-Université de Toulouse (UT)-Institut National de la Santé et de la Recherche Médicale (INSERM), CEA Tech en régions (CEA-TECH-Reg), 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), Service de Dermatologie (CHU de Dijon), Université de Reims Champagne-Ardenne (URCA), Institut d'Aménagement des Territoires, d'Environnement et d'Urbanisme de l'Université de Reims (IATEUR), HABITER - EA 2076 (HABITER), Université de Reims Champagne-Ardenne (URCA)-Maison des Sciences Humaines de Champagne-Ardenne (MSH-URCA), and Université de Reims Champagne-Ardenne (URCA)-Université de Reims Champagne-Ardenne (URCA)
Subjects: Ichtyoses héréditaires, [MATH.MATH-ST]Mathematics [math]/Statistics [math.ST], Méthode de capture-recapture, Dermatology, [MATH.MATH-ST] Mathematics [math]/Statistics [math.ST], ComputingMilieux_MISCELLANEOUS, Prévalence
Abstract: International audience
Published: 2012

43. Hypoxia and MITF control metastatic behaviour in mouse and human melanoma cells

Author: Maryline Allegra, Sandy Giuliano, Robert Ballotti, Jean-Philippe Lacour, Véronique Hofman, Corine Bertolotto, Philippe Bahadoran, Yann Cheli, Sophie Tartare-Deckert, Paul Hofman, Nina Fenouille, BERTOLOTTO-BALLOTTI, BERTOLOTTO-BALLOTTI, Centre méditérannéen de médecine moléculaire (C3M), Université Nice Sophia Antipolis (1965 - 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), ERI-21/EA 4319, Laboratoire de Pathologie Clinique et Expérimentale et CRB INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Louis Pasteur [Chartres]-Université de Nice Sophia-Antipolis (UNSA), Service de Dermatologie [Nice], Hôpital Archet 2 [Nice] (CHU), and Université Nice Sophia Antipolis (... - 2019) (UNS)
Subjects: Cancer Research, Skin Neoplasms, Population, Melanoma, Experimental, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Metastasis, Mesoderm, 03 medical and health sciences, Mice, 0302 clinical medicine, Melanocyte differentiation, [SDV.CAN] Life Sciences [q-bio]/Cancer, Genetics, medicine, Basic Helix-Loop-Helix Transcription Factors, Gene silencing, Animals, Humans, Neoplasm Invasiveness, Gene Silencing, Neoplasm Metastasis, education, Molecular Biology, Transcription factor, Melanoma, 030304 developmental biology, 0303 health sciences, education.field_of_study, Microphthalmia-Associated Transcription Factor, integumentary system, Mesenchymal stem cell, medicine.disease, Microphthalmia-associated transcription factor, Hypoxia-Inducible Factor 1, alpha Subunit, Cell Hypoxia, 3. Good health, 030220 oncology & carcinogenesis, Immunology, Cancer research
Abstract: International audience; Melanomas are very aggressive neoplasms with notorious resistance to therapeutics. It was recently proposed that the remarkable phenotypic plasticity of melanoma cells allows for the rapid development of both resistance to chemotherapeutic drugs and invasive properties. Indeed, the capacity of melanoma cells to form distant metastases is the main cause of mortality in melanoma patients. Therefore, the identification of the mechanism controlling melanoma phenotype is of paramount importance. In the present report, we show that deletion of microphthalmia-associated transcription factor (MITF), the master gene in melanocyte differentiation, is sufficient to increase the metastatic potential of mouse and human melanoma cells. MITF silencing also increases fibronectin and Snail, two mesenchymal markers that might explain the increased invasiveness in vitro and in vivo. Furthermore, ablation of this population by Forskolin-induced differentiation or MITF-forced expression significantly decreases tumour and metastasis formation, suggesting that eradication of low-MITF cells might improve melanoma treatment. Moreover, we demonstrate that a hypoxic microenvironment decreases MITF expression through an indirect, hypoxia-inducible factor 1 (HIF1)α-dependant transcriptional mechanism, and increases the tumourigenic and metastatic properties of melanoma cells. We identified Bhlhb2, a new factor in melanoma biology, as the mediator of hypoxia/HIF1α inhibitory effect on MITF expression. Our results reveal a hypoxia-HIF1α-BHLHB2-MITF cascade controlling the phenotypic plasticity in melanoma cells and favouring metastasis development. Targeting this pathway might be helpful in the design of new anti-melanoma therapies.
Published: 2011

44. Senescent cells develop a PARP-1 and nuclear factor-{kappa}B-associated secretome (PNAS)

Author: Corine Bertolotto, Mickaël Ohanna, Brigitte Bressac-de Paillerets, Jean-François Peyron, Véronique Imbert, Stéphane Rocchi, Jean-Philippe Lacour, Robert Ballotti, Caroline Bonet, Joséphine Zangari, Caroline Robert, Karine Bille, Véronique Hofman, Paul Hofman, Sandy Giuliano, Centre méditérannéen de médecine moléculaire (C3M), 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), Institut Gustave Roussy (IGR), Service de Dermatologie [Nice], Hôpital Archet 2 [Nice] (CHU), BERTOLOTTO-BALLOTTI, BERTOLOTTO-BALLOTTI, and Université Nice Sophia Antipolis (1965 - 2019) (UNS)
Subjects: Senescence, Chemokine, Poly (ADP-Ribose) Polymerase-1, [SDV.CAN]Life Sciences [q-bio]/Cancer, CCL2, Article, 03 medical and health sciences, 0302 clinical medicine, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cell Line, Tumor, Genetics, Humans, Neoplasm Invasiveness, Melanoma, Cellular Senescence, Chemokine CCL2, 030304 developmental biology, 0303 health sciences, Tumor microenvironment, biology, Effector, Gene Expression Profiling, NF-kappa B, Secretomics, 3. Good health, Cell biology, Gene Expression Regulation, Neoplastic, 030220 oncology & carcinogenesis, biology.protein, Signal transduction, Poly(ADP-ribose) Polymerases, Cell aging, Developmental Biology, Research Paper, DNA Damage, Signal Transduction
Abstract: International audience; Melanoma cells can enter the process of senescence, but whether they express a secretory phenotype, as reported for other cells, is undetermined. This is of paramount importance, because this secretome can alter the tumor microenvironment and the response to chemotherapeutic drugs. More generally, the molecular events involved in formation of the senescent-associated secretome have yet to be determined. We reveal here that melanoma cells experiencing senescence in response to diverse stimuli, including anti-melanoma drugs, produce an inflammatory secretory profile, where the chemokine ligand-2 (CCL2) acts as a critical effector. Thus, we reveal how senescence induction might be involved in therapeutic failure in melanoma. We further provide a molecular relationship between senescence induction and secretome formation by revealing that the poly(ADP-ribose) polymerase-1 (PARP-1)/nuclear factor-κB (NF-κB) signaling cascade, activated during senescence, drives the formation of a secretome endowed with protumoral and prometastatic properties. Our findings also point to the existence of the PARP-1 and NF-κB-associated secretome, termed the PNAS, in nonmelanoma cells. Most importantly, inhibition of PARP-1 or NF-κB prevents the proinvasive properties of the secretome. Collectively, identification of the PARP-1/NF-κB axis in secretome formation opens new avenues for therapeutic intervention against cancers.
Published: 2011

45. Mitf is the key molecular switch between mouse or human melanoma initiating cells and their differentiated progeny

Author: S Guiliano, Véronique Hofman, Stéphane Rocchi, Thomas Botton, Robert Ballotti, Yann Cheli, Paul Hofman, Philippe Bahadoran, Corine Bertolotto, Centre méditérannéen de médecine moléculaire (C3M), 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), ERI-21/EA 4319, Laboratoire de Pathologie Clinique et Expérimentale et CRB INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Louis Pasteur [Chartres]-Université de Nice Sophia-Antipolis (UNSA), Service de Dermatologie [Nice], Hôpital Archet 2 [Nice] (CHU), BERTOLOTTO-BALLOTTI, BERTOLOTTO-BALLOTTI, and Université Nice Sophia Antipolis (1965 - 2019) (UNS)
Subjects: Homeobox protein NANOG, Cancer Research, Skin Neoplasms, Population, Melanoma, Experimental, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Stem cell marker, 03 medical and health sciences, Mice, 0302 clinical medicine, Melanocyte differentiation, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cell Line, Tumor, Genetics, medicine, Animals, Humans, Gene Silencing, education, Molecular Biology, Melanoma, neoplasms, 030304 developmental biology, 0303 health sciences, education.field_of_study, Microphthalmia-Associated Transcription Factor, Cell Differentiation, Microphthalmia-associated transcription factor, medicine.disease, Mice, Inbred C57BL, 030220 oncology & carcinogenesis, Lymphatic Metastasis, Immunology, Cancer cell, Cell Transdifferentiation, Cancer research, Neoplastic Stem Cells, CDK inhibitor, Cell Division, Cyclin-Dependent Kinase Inhibitor p27, Neoplasm Transplantation
Abstract: International audience; In melanoma, as well as in other solid tumors, the cells within a given tumor exhibit strong morphological, functional and molecular heterogeneity that might reflect the existence of different cancer cell populations, among which are melanoma-initiating cells (MICs) with 'stemness' properties and their differentiated, fast-growing progeny. The existence of a slow-growing population might explain the resistance of melanoma to classical chemotherapies that target fast growing cells. Therefore, elucidating the biologic properties of MICs and, more importantly, the molecular mechanisms that drive the transition between MICs and their proliferating progeny needs to be addressed to develop an efficient melanoma therapy. Using B16 mouse melanoma cells and syngeneic mice, we show that the inhibition of microphthalmia-associated transcription factor (Mitf), the master regulator of melanocyte differentiation, increases the tumorigenic potential of melanoma cells and upregulates the stem cell markers Oct4 and Nanog. Notably, p27, the CDK inhibitor, is increased in Mitf-depleted cells and is required for exacerbation of the tumorigenic properties of melanoma cells. Further, a slow-growing population with low-Mitf level and high tumorigenic potential exists spontaneously in melanoma. Ablation of this population dramatically decreases tumor formation. Importantly, these data were confirmed using human melanoma cell lines and freshly isolated human melanoma cell from lymph node and skin melanoma metastasis. Taken together our data, identified Mitf and p27 as the key molecular switches that control the transition between MICs and their differentiated progeny. Eradication of low-Mitf cells might be an appealing strategy to cure melanoma.
Published: 2011

46. Advances in melanoma senescence and potential clinical application

Author: Giuliano, Sandy, Ohanna, Mickaël, Ballotti, Robert, Bertolotto, Corine, Centre méditérannéen de médecine moléculaire (C3M), 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), Service de Dermatologie [Nice], Hôpital Archet 2 [Nice] (CHU), BERTOLOTTO-BALLOTTI, BERTOLOTTO-BALLOTTI, and Université Nice Sophia Antipolis (1965 - 2019) (UNS)
Subjects: Cyclin-Dependent Kinase Inhibitor p21, Oncogene Proteins, Microphthalmia-Associated Transcription Factor, Chromosomal Proteins, Non-Histone, Tumor Suppressor Proteins, Cell Cycle, Intracellular Signaling Peptides and Proteins, [SDV.CAN]Life Sciences [q-bio]/Cancer, Oncogenes, Protein-Tyrosine Kinases, Senescence, Proto-Oncogene Proteins c-myc, Phenotype, [SDV.CAN] Life Sciences [q-bio]/Cancer, Humans, Syk Kinase, Poly-ADP-Ribose Binding Proteins, T-Box Domain Proteins, Melanoma, Biomarkers, Cellular Senescence, Cell Proliferation
Abstract: International audience; Normal cells possess a limited proliferative life span, after which they enter a state of irreversible growth arrest, called replicative senescence, which acts as a potent barrier against transformation. Transformed cells have escaped the process of replicative senescence and theoretically can not re-enter senescence. However, recent observations showed that transformed cells, and particularly the melanoma cells, can still undergo oncogene or stress-induced senescence. This senescence state is accompanied by many of the markers associated with replicative senescence, such as flattened shape, increased acidic β-galactosidase activity, characteristic changes in gene expression and growth arrest. Interestingly, in some cancers, senescence induction following chemotherapy has been correlated with a favorable patient outcome. In this review, we gathered recent results describing senescence-like phenotype induction in melanoma cells and discuss why senescence may also be exploited as a therapeutic strategy in melanoma.
Published: 2010

47. Microphthalmia-associated transcription factor controls the DNA damage response and a lineage-specific senescence program in melanomas

Author: Sandy Giuliano, Gilles Ponzio, Laurent Beuret, Mickaël Ohanna, Karine Bille, Corine Bertolotto, Caroline Bonet, Agnès Loubat, Robert Ballotti, Philippe Bahadoran, Paul Hofman, Véronique Hofman, Yann Cheli, Centre méditérannéen de médecine moléculaire (C3M), 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), Biologie et physiopathologie cutanées : expression génique, signalisation et thérapie, COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-IFR50-Institut National de la Santé et de la Recherche Médicale (INSERM), ERI-21/EA 4319, Laboratoire de Pathologie Clinique et Expérimentale et CRB INSERM, Institut National de la Santé et de la Recherche Médicale (INSERM)-Hôpital Louis Pasteur [Chartres]-Université de Nice Sophia-Antipolis (UNSA), Service de Dermatologie [Nice], Hôpital Archet 2 [Nice] (CHU), Université Nice Sophia Antipolis (1965 - 2019) (UNS), and BERTOLOTTO-BALLOTTI, BERTOLOTTO-BALLOTTI
Subjects: Senescence, Cancer Research, DNA damage, Melanoma, Experimental, Mitosis, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, 03 medical and health sciences, Mice, 0302 clinical medicine, Downregulation and upregulation, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cell Line, Tumor, medicine, Animals, Humans, Cell Lineage, Transcription factor, Melanoma, Cellular Senescence, 030304 developmental biology, 0303 health sciences, Microphthalmia-Associated Transcription Factor, integumentary system, Microphthalmia-associated transcription factor, medicine.disease, body regions, Oncology, 030220 oncology & carcinogenesis, Cancer cell, Cancer research, Signal transduction, Tumor Suppressor Protein p53, DNA Damage, Signal Transduction
Abstract: Apoptosis and senescence are cellular failsafe programs that counteract excessive mitogenic signaling observed in cancer cells. Melanoma is known for its notorious resistance to apoptotic processes; therefore, senescence, which remains poorly understood in melanomas, can be viewed as a therapeutic alternative. Microphthalmia-associated transcription factor (MITF), in which its M transcript is specifically expressed in melanocyte cells, plays a critical role in melanoma proliferation, and its specific inhibition is associated with G0-G1 growth arrest. Interestingly, decreased MITF expression has been described in senescent melanocytes, and we have observed an inhibition of MITF expression in melanoma cells exposed to chemotherapeutic drugs that induce their senescence. All these observations thereby question the role of MITF in controlling senescence in melanoma cells. Here, we report that long-term depletion of MITF in melanoma cells triggers a senescence program characterized by typical morphologic and biochemical changes associated with a sustained growth arrest. Further, we show that MITF-silenced cells engage a DNA damage response (DDR) signaling pathway, leading to p53 upregulation, which is critically required for senescence entry. This study uncovers the existence of a lineage-restricted DDR/p53 signaling pathway that is inhibited by MITF to prevent senescence and favor melanoma cell proliferation. Cancer Res; 70(9); 3813–22. ©2010 AACR.
Published: 2010

48. Microphthalmia-associated Transcription Factor Regulates RAB27A Gene Expression and Controls Melanosome Transport

Author: Jean Paul Ortonne, Roser Buscà, Christine Chiaverini, Laurent Beuret, Enrica Flori, Corine Bertolotto, Robert Ballotti, Karine Bille, Philippe Bahadoran, Patricia Abbe, Service de Dermatologie [Nice], Hôpital Archet 2 [Nice] (CHU), Biologie et pathologies des cellules mélanocytaires : de la pigmentation cutanée aux mélanomes, Université Nice Sophia Antipolis (... - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-IFR50-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Centre méditerranéen de médecine moléculaire (C3M), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-Université Côte d'Azur (UCA)-Institut National de la Santé et de la Recherche Médicale (INSERM), Department of Dermatology, and Centre Hospitalier Universitaire de Nice (CHU Nice)
Subjects: endocrine system, Transcription, Genetic, [SDV]Life Sciences [q-bio], Molecular Sequence Data, Myosin Type V, Biology, Biochemistry, rab27 GTP-Binding Proteins, E-Box Elements, 03 medical and health sciences, Mice, 0302 clinical medicine, Melanocyte differentiation, Cell Line, Tumor, Transcriptional regulation, STXBP1, Animals, Humans, Gene Silencing, Promoter Regions, Genetic, Molecular Biology, Transcription factor, ComputingMilieux_MISCELLANEOUS, 030304 developmental biology, Melanosome, Adaptor Proteins, Signal Transducing, Regulation of gene expression, 0303 health sciences, Microphthalmia-Associated Transcription Factor, Melanosomes, integumentary system, Base Sequence, Biological Transport, Cell Biology, Microphthalmia-associated transcription factor, Molecular biology, Actins, body regions, Gene Expression Regulation, Neoplastic, Melanosome transport, rab GTP-Binding Proteins, 030220 oncology & carcinogenesis, Protein Binding
Abstract: Melanosomes are lysosome-related organelles specialized in melanin synthesis and transport. In this study, we show that microphthalmia-associated transcription factor (MITF) silencing induces melanosome gathering around the nucleus and causes the relocalization of Rab27A, Slac2a-Mlph, and Myo5a that control the transport of melanosomes on the actin network. In an attempt to elucidate the mechanism by which MITF controls melanosome distribution, we identify RAB27A as a new MITF target gene. Indeed, MITF silencing leads to a dramatic decrease in Rab27A expression and blocks the stimulation of Rab27A expression evoked by cAMP. Further, forced expression of MITF increases Rab27A expression, indicating that MITF is required and sufficient for Rab27A expression in melanoma cells. MITF binds to two E-boxes in the proximal region of the Rab27A promoter and stimulates its transcriptional activity. Finally, re-expression of Rab27A, in MITF-depleted cells, restores the transport of melanosomes to the cell periphery. These results show that RAB27A is a new direct transcriptional target of MITF and link MITF to melanosome transport, another key parameter of melanocyte differentiation and skin pigmentation. Interestingly, Rab27A is involved in other fundamental physiological functions, such as the transport of lytic granules and insulin secretion. Thus our results, deciphering the mechanism of Rab27A transcriptional regulation, have an interest that goes beyond the skin pigmentation field.
Published: 2008

49. Cyclic AMP promotes a peripheral distribution of melanosomes and stimulates melanophilin/Slac2-a and actin association

Author: Bertolotto-Ballotti, Bertolotto-Ballotti, Passeron, Thierry, Bahadoran, Philippe, Bertolotto, Corine, Chiaverini, Christine, Buscà, Roser, Valony, Gaëlle, Bille, Karine, Ortonne, Jean‐paul, Ballotti, Robert, COMUE Université Côte d'Azur (2015-2019) (COMUE UCA), Service de Dermatologie [Nice], Hôpital Archet 2 [Nice] (CHU), Biologie et pathologies des cellules mélanocytaires : de la pigmentation cutanée aux mélanomes, Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-IFR50-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Service de Dermatologie, Centre Hospitalier Universitaire de Nice (CHU Nice)-Hôpital l'Archet, Centre méditérannéen de médecine moléculaire (C3M), 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), BERTOLOTTO-BALLOTTI, BERTOLOTTO-BALLOTTI, and Université Nice Sophia Antipolis (... - 2019) (UNS)
Subjects: Myosin Type V, Melanoma, Experimental, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Protein Serine-Threonine Kinases, Biochemistry, rab27 GTP-Binding Proteins, Cell Line, 03 medical and health sciences, Mice, GTP-binding protein regulators, [SDV.CAN] Life Sciences [q-bio]/Cancer, Cell Line, Tumor, Myosin, Genetics, Cyclic AMP, Animals, Humans, Cytoskeleton, Molecular Biology, ComputingMilieux_MISCELLANEOUS, Actin, 030304 developmental biology, Melanosome, Adaptor Proteins, Signal Transducing, 0303 health sciences, rho-Associated Kinases, Melanosomes, Myosin Heavy Chains, 030302 biochemistry & molecular biology, Cell Membrane, Colforsin, Intracellular Signaling Peptides and Proteins, Dendrites, Cyclic AMP-Dependent Protein Kinases, Actins, Cell biology, Melanosome transport, alpha-MSH, rab GTP-Binding Proteins, Melanophilin, cAMP-dependent pathway, Carrier Proteins, rhoA GTP-Binding Protein, Biotechnology, Protein Binding
Abstract: Melanosomes are melanin-containing organelles that belong to a recently individualized group of lysosome-related organelles. Recently, numerous reports have dissected the molecular mechanisms that control melanosome transport, but nothing was known about the possible regulation of melanosome distribution by exogenous physiological stimulus. In the present report, we demonstrate that a physiological melanocyte-differentiating agent such as alpha-melanocyte-stimulating hormone, through the stimulation of the cAMP pathway, induces a rapid centrifugal transport of melanosomes, leading to their accumulation at the dendrite tips of melanocytes. Interestingly, the small GTP binding proteins of the p21Rho family and one of their effectors, p160 Rho-associated kinase, but not PKA, play a key role in redistribution of melanosomes at the extremities of the dendrites. Further, we have investigated, at the molecular level, the effect of cAMP on the different proteins involved in the control of melanosome transport. We demonstrate that cAMP stimulates the expression of Rab27a and rapidly increases the interaction of the melanophilin/Slac2-a with actin. Thus, we propose that the stimulation of the interaction between melanophilin/Slac2-a and actin would allow the rapid accumulation of melanosomes in the actin-rich region of the dendrite extremities.
Published: 2004

50. Tumor necrosis factor alpha-mediated inhibition of melanogenesis is dependent on nuclear factor kappa B activation

Author: Bertolotto-Ballotti, Bertolotto-Ballotti, Englaro, Walter, Bahadoran, Philippe, Bertolotto, Corine, Buscà, Roser, Derijard, Benoit, Livolsi, Antonia, Peyron, Jean-François, Ortonne, Jean-Paul, Ballotti, Robert, BERTOLOTTO-BALLOTTI, BERTOLOTTO-BALLOTTI, Service de Dermatologie [Nice], Hôpital Archet 2 [Nice] (CHU), Biologie et pathologies des cellules mélanocytaires : de la pigmentation cutanée aux mélanomes, Université Nice Sophia Antipolis (1965 - 2019) (UNS), COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-COMUE Université Côte d'Azur (2015-2019) (COMUE UCA)-IFR50-Institut National de la Santé et de la Recherche Médicale (INSERM)-Université Côte d'Azur (UCA), Institut de Biologie Valrose (IBV), 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)-Centre National de la Recherche Scientifique (CNRS)-Université Côte d'Azur (UCA), Centre méditérannéen de médecine moléculaire (C3M), 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), Department of Dermatology, Centre Hospitalier Universitaire de Nice (CHU Nice), Université Nice Sophia Antipolis (... - 2019) (UNS), and 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)-Université Côte d'Azur (UCA)-Centre National de la Recherche Scientifique (CNRS)
Subjects: Cancer Research, Transcription, Genetic, Tyrosinase, medicine.medical_treatment, Melanoma, Experimental, Apoptosis, Melanin, Mice, 0302 clinical medicine, Genes, Reporter, Cyclic AMP, Tumor Cells, Cultured, Ultraviolet light, Promoter Regions, Genetic, ComputingMilieux_MISCELLANEOUS, 0303 health sciences, Monophenol Monooxygenase, NF-kappa B, 3T3 Cells, DNA, Neoplasm, Neoplasm Proteins, Cell biology, DNA-Binding Proteins, Gene Expression Regulation, Neoplastic, Cytokine, Depression, Chemical, Enzyme Induction, 030220 oncology & carcinogenesis, I-kappa B Proteins, Tumor necrosis factor alpha, Signal transduction, medicine.medical_specialty, [SDV.CAN]Life Sciences [q-bio]/Cancer, Biology, Transfection, 03 medical and health sciences, [SDV.CAN] Life Sciences [q-bio]/Cancer, Internal medicine, Genetics, medicine, Animals, Molecular Biology, Transcription factor, 030304 developmental biology, Melanins, Tumor Necrosis Factor-alpha, Colforsin, NFKB1, Transcription Factor AP-1, Endocrinology
Abstract: Melanogenesis is a physiological process resulting in the synthesis of melanin pigments which play a crucial protective role against skin photocarcinogenesis. In vivo, solar ultraviolet light triggers the secretion of numerous keratinocyte-derived factors that are implicated in the regulation of melanogenesis. Among these, tumor necrosis factor alpha (TNFalpha), a cytokine implicated in the pro-inflammatory response, down-regulates pigment synthesis in vitro. In this report, we aimed to determine the molecular mechanisms by which this cytokine inhibits melanogenesis in B16 melanoma cells. First, we show that TNFalpha inhibits the activity and protein expression of tyrosinase which is the key enzyme of melanogenesis. Further, we demonstrate that this effect is subsequent to a down-regulation of the tyrosinase promoter activity in both basal and cAMP-induced melanogenesis. Finally, we present evidence indicating that the inhibitory effect of TNFalpha on melanogenesis is dependent on nuclear factor kappa B (NFkappaB) activation. Indeed, overexpression of this transcription factor in B16 cells is sufficient to inhibit tyrosinase promoter activity. Furthermore, a mutant of inhibitory kappa B (IkappaB), that prevents NFkappaB activation, is able to revert the effect of TNFalpha on the tyrosinase promoter activity. Taken together, our results clarify the mechanisms by which TNFalpha inhibits pigmentation and point out the key role of NFkappaB in the regulation of melanogenesis.
Published: 1999

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