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1. Bronchial hyperresponsiveness, airway inflammation, and reversibility in patients with chronic obstructive pulmonary disease

Author

Zanini A, Cherubino F, Zampogna E, Croce S, Pignatti P, and Spanevello A

Subjects
Diseases of the respiratory system, RC705-779
Abstract

Andrea Zanini,1 Francesca Cherubino,1 Elisabetta Zampogna,1 Stefania Croce,2 Patrizia Pignatti,2 Antonio Spanevello3 1Division of Pneumology, IRCCS Rehabilitation Institute of Tradate, Salvatore Maugeri Foundation (IRCCS), Tradate, Italy; 2Allergy and Immunology Unit, Salvatore Maugeri Foundation (IRCCS), Pavia, Italy; 3Department of Clinical and Experimental Medicine, University of Insubria, Varese, Italy Background: Bronchial hyperresponsiveness (BHR), sputum eosinophilia, and bronchial reversibility are often thought to be a hallmark of asthma, yet it has been shown to occur in COPD as well.Objectives: To evaluate the relationship between BHR, lung function, and airway inflammation in COPD patients.Methods: Thirty-one, steroid-free patients with stable, mild and moderate COPD were studied. The following tests were carried out: baseline lung function, reversibility, provocative dose of methacholine causing a 20% fall in forced expiratory volume in 1 second, a COPD symptom score, and sputum induction.Results: Twenty-nine patients completed the procedures. About 41.4% had BHR, 31.0% had increased sputum eosinophils, and 37.9% had bronchial reversibility. Some of the patients had only one of these characteristics while others had two or the three of them. Patients with BHR had higher sputum eosinophils than patients without BHR (P=0.046) and those with sputum eosinophils ≥3% had more exacerbations in the previous year and a higher COPD symptom score than patients with sputum eosinophils

Published
2015

2. ESGO–ESMO–ESP consensus conference recommendations on ovarian cancer: pathology and molecular biology and early, advanced and recurrent disease

Author

Ledermann, J.A., Matias-Guiu, X., Amant, F., Concin, N., Davidson, B., Fotopoulou, C., González-Martin, A., Gourley, C., Leary, A., Lorusso, D., Banerjee, S., Chiva, L., Cibula, D., Colombo, N., Croce, S., Eriksson, A.G., Falandry, C., Fischerova, D., Harter, P., Joly, F., Lazaro, C., Lok, C., Mahner, S., Marmé, F., Marth, C., McCluggage, W.G., McNeish, I.A., Morice, P., Nicum, S., Oaknin, A., Pérez-Fidalgo, J.A., Pignata, S., Ramirez, P.T., Ray-Coquard, I., Romero, I., Scambia, G., Sehouli, J., Shapira-Frommer, R., Sundar, S., Tan, D.S.P., Taskiran, C., van Driel, W.J., Vergote, I., Planchamp, F., Sessa, C., and Fagotti, A.

Published
2024
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9. Safety of COVID-19 Vaccines Among the Paediatric Population: Analysis of the European Surveillance Systems and Pivotal Clinical Trials

Author

Ahmadizar F., Luxi N., Raethke M., Schmikli S., Riefolo F., Saraswati P. W., Bucsa C., Osman A., Liddiard M., Maques F. B., Petrelli G., Sonderlichova S., Thurin N. H., Villalobos F., Trifiro G., Sturkenboom M., Moretti U., Bellitto C., Ciccimarra F., Gonella L. A., Arzenton E., Chiamulera C., Lora R., Bellantuono D., Sabaini A., Firenze A., Zodda D., Guidotti F., Zappone M., Alagna B., Cutroneo P. M., Minore C., Costantino C., Vitale F., D'Alessandro G., Morreale I., Marsala L., Farinella D., Bavetta S., Fantini M. P., Reno C., Raschi E., Poluzzi E., Sapigni E., Potenza A. M., Podetti D., Nikitina V., Ricciardelli R., Mogheiseh N., Croce S., Paltrinieri B., Castellani S., Sangiorgi E., Selleri M., Lucchesi S., Catucci G., Savini D., Sacripanti C., Faccioli M., Romio M. S., Rossi L., Radici S., Negri G., Fares L., Ajolfi C., Fadda A., Chiarello A., Pieraccini F., Gavioli B., Palazzi S., Tuccori M., Vannacci A., Bonaiuti R., Ravaldi C., Lombardi N., Crescioli G., Gori F., Tessari R., Zandona E., Zanoni G., Senna G., Crivellaro M. A., Cancian M., Venturini F., Ferri M., Leonardi L., Orzetti S., Caccin E., Baldo P., Capuano A., Rafaniello C., Ferrajolo C., Pagliaro C., Mercaldo M., di Giorgio A., Tari M., Manna S., Farina G., Di Mauro C., De Carlo I., Senesi I., Pileggi C., Palleria C., Gallelli L., De Sarro G., de Sarro C., Verduci C., Papadopoli R., Trabace L., Morgese M., Schiavone S., Tucci P., Bove M., Lapi F., Cricelli C., Racagni G., Tonolo S., Fava G., Giuffrida S., Amato V., Gambera M., Montresor V., Mastropasqua D., Ahmadizar F., Luxi N., Raethke M., Schmikli S., Riefolo F., Saraswati P.W., Bucsa C., Osman A., Liddiard M., Maques F.B., Petrelli G., Sonderlichova S., Thurin N.H., Villalobos F., Trifiro G., Sturkenboom M., Moretti U., Bellitto C., Ciccimarra F., Gonella L.A., Arzenton E., Chiamulera C., Lora R., Bellantuono D., Sabaini A., Firenze A., Zodda D., Guidotti F., Zappone M., Alagna B., Cutroneo P.M., Minore C., Costantino C., Vitale F., D'Alessandro G., Morreale I., Marsala L., Farinella D., Bavetta S., Fantini M.P., Reno C., Raschi E., Poluzzi E., Sapigni E., Potenza A.M., Podetti D., Nikitina V., Ricciardelli R., Mogheiseh N., Croce S., Paltrinieri B., Castellani S., Sangiorgi E., Selleri M., Lucchesi S., Catucci G., Savini D., Sacripanti C., Faccioli M., Romio M.S., Rossi L., Radici S., Negri G., Fares L., Ajolfi C., Fadda A., Chiarello A., Pieraccini F., Gavioli B., Palazzi S., Tuccori M., Vannacci A., Bonaiuti R., Ravaldi C., Lombardi N., Crescioli G., Gori F., Tessari R., Zandona E., Zanoni G., Senna G., Crivellaro M.A., Cancian M., Venturini F., Ferri M., Leonardi L., Orzetti S., Caccin E., Baldo P., Capuano A., Rafaniello C., Ferrajolo C., Pagliaro C., Mercaldo M., di Giorgio A., Tari M., Manna S., Farina G., Di Mauro C., De Carlo I., Senesi I., Pileggi C., Palleria C., Gallelli L., De Sarro G., de Sarro C., Verduci C., Papadopoli R., Trabace L., Morgese M., Schiavone S., Tucci P., Bove M., Lapi F., Cricelli C., Racagni G., Tonolo S., Fava G., Giuffrida S., Amato V., Gambera M., Montresor V., and Mastropasqua D.

Subjects
COVID-19 Vaccines, safety, Surveillance Systems, Pivotal Clinical Trials
Abstract

Background and Objectives: The European Medicine Agency extended the use of Comirnaty, Spikevax, and Nuvaxovid in paediatrics; thus, these vaccines require additional real-world safety evidence. Herein, we aimed to monitor the safety of COVID-19 vaccines through Covid-19 Vaccine Monitor (CVM) and EudraVigilance surveillance systems and the published pivotal clinical trials. Methods: In a prospective cohort of vaccinees aged between 5 and 17 years, we measured the frequency of commonly reported (local/systemic solicited) and serious adverse drug events (ADRs) following the first and second doses of COVID-19 vaccines in Europe using data from the CVM cohort until April 2022. The results of previous pivotal clinical trials and data in the EudraVigilance were also analysed. Results: The CVM study enrolled 658 first-dose vaccinees (children aged 5–11 years; n = 250 and adolescents aged 12–17 years; n = 408). Local/systemic solicited ADRs were common, whereas serious ADRs were uncommon. Among Comirnaty first and second dose recipients, 28.8% and 17.1% of children and 54.2% and 52.2% of adolescents experienced at least one ADR, respectively; injection-site pain (29.2% and 20.7%), fatigue (16.1% and 12.8%), and headache (22.1% and 19.3%) were the most frequent local and systemic ADRs. Results were consistent but slightly lower than in pivotal clinical trials. Reporting rates in Eudravigilance were lower by a factor of 1000. Conclusions: The CVM study showed high frequencies of local solicited reactions after vaccination but lower rates than in pivotal clinical trials. Injection-site pain, fatigue, and headache were the most commonly reported ADRs for clinical trials, but higher than spontaneously reported data.

Published
2023

12. Large-Scale Postmarketing Surveillance of Biological Drugs for Immune-Mediated Inflammatory Diseases Through an Italian Distributed Multi-Database Healthcare Network: The VALORE Project

Author

Trifiro, G., Isgro, V., Ingrasciotta, Y., Ientile, V., L'Abbate, L., Foti, S. S., Belleudi, V., Poggi, F., Fontana, A., Moretti, U., Lora, R., Sabaini, A., Senesi, I., Sorrentino, C., Puzo, M. R., Padula, A., Fusco, M., Giordana, R., Solfrini, V., Puccini, A., Rossi, P., Del Zotto, S., Leoni, O., Zanforlini, M., Ancona, D., Bavaro, V., Garau, D., Ledda, S., Scondotto, S., Allotta, A., Tuccori, M., Gini, R., Bucaneve, G., Franchini, D., Cavazzana, A., Biasi, V., Spila Alegiani, S., Massari, M., Andretta, I., Tanaglia, M., Carriero, A., Sassano, S., De Sarro, G., Mirarchi, S., Palleria, C., Sarro, C., Balestrieri, M., Rostan, S., Capuano, A., Bernardi, F. F., Trama, U., Russo, A., Fumo, M. G., Addis, A., Musicco, F., Sapigni, E., Mazzetti, I., Podetti, D., Potenza, A. M., Nikitina, V., Ricciardelli, R., Mogheiseh, N., Croce, S., Pettinelli, A., Ejlli, L., Fortino, I., Ercolanoni, M., Mazzone, A., Nisic, A., Schiatti, S., Ludergnani, M., Mancini, M., Patregnani, L., Fabbietti, P., Antonicelli, E., Mangano, A., Campomori, A., Urru, S. A., Costa, G., Guarrera, G. M., Stella, P., Serra, E., Carta, P., Vannacci, A., Lucenteforte, E., Parrilli, M., Convertino, I., De Giorgi, M., Rocchi, R. E., Rossi, M., Scroccaro, G., Deambrosis, P., Grindelli, G., Ferroni, E., Trifiro, G., Isgro, V., Ingrasciotta, Y., Ientile, V., L'Abbate, L., Foti, S. S., Belleudi, V., Poggi, F., Fontana, A., Moretti, U., Lora, R., Sabaini, A., Senesi, I., Sorrentino, C., Puzo, M. R., Padula, A., Fusco, M., Giordana, R., Solfrini, V., Puccini, A., Rossi, P., Del Zotto, S., Leoni, O., Zanforlini, M., Ancona, D., Bavaro, V., Garau, D., Ledda, S., Scondotto, S., Allotta, A., Tuccori, M., Gini, R., Bucaneve, G., Franchini, D., Cavazzana, A., Biasi, V., Spila Alegiani, S., Massari, M., Andretta, I., Tanaglia, M., Carriero, A., Sassano, S., De Sarro, G., Mirarchi, S., Palleria, C., Sarro, C., Balestrieri, M., Rostan, S., Capuano, A., Bernardi, F. F., Trama, U., Russo, A., Fumo, M. G., Addis, A., Musicco, F., Sapigni, E., Mazzetti, I., Podetti, D., Potenza, A. M., Nikitina, V., Ricciardelli, R., Mogheiseh, N., Croce, S., Pettinelli, A., Ejlli, L., Fortino, I., Ercolanoni, M., Mazzone, A., Nisic, A., Schiatti, S., Ludergnani, M., Mancini, M., Patregnani, L., Fabbietti, P., Antonicelli, E., Mangano, A., Campomori, A., Urru, S. A., Costa, G., Guarrera, G. M., Stella, P., Serra, E., Carta, P., Vannacci, A., Lucenteforte, E., Parrilli, M., Convertino, I., De Giorgi, M., Rocchi, R. E., Rossi, M., Scroccaro, G., Deambrosis, P., Grindelli, G., and Ferroni, E.

Subjects
Male, medicine.medical_specialty, Population, Postmarketing surveillance, Rate ratio, REGISTRIES, Retrospective Studie, Internal medicine, BIOSIMILARS, medicine, Adalimumab, Humans, Pharmacology (medical), Original Research Article, education, Adverse effect, ANTI-TNF THERAPY, RHEUMATOID-ARTHRITIS, RISK, PHARMACOVIGILANCE, BIOSIMILARS, EXPERIENCE, REGISTRIES, PSORIASIS, MEDICINES, ACCESS, Biosimilar Pharmaceuticals, Retrospective Studies, RISK, Delivery of Health Care, Female, Infliximab, Italy, SARS-CoV-2, COVID-19, Pharmacology, education.field_of_study, PSORIASIS, business.industry, Biosimilar, ANTI-TNF THERAPY, General Medicine, medicine.disease, RHEUMATOID-ARTHRITIS, PHARMACOVIGILANCE, MEDICINES, EXPERIENCE, Immune-mediated inflammatory diseases, ACCESS, business, Human, Biosimilar Pharmaceutical, Biotechnology, medicine.drug
Abstract

Background Biological drugs have improved the management of immune-mediated inflammatory diseases (IMIDs) despite being associated with important safety issues such as immunogenicity, infections, and malignancies in real-world settings. Objective The aim of this study was to explore the potential of a large Italian multi-database distributed network for use in the postmarketing surveillance of biological drugs, including biosimilars, in patients with IMID. Methods A retrospective cohort study was conducted using 13 Italian regional claims databases during 2010–2019. A tailor-made R-based tool developed for distributed analysis of claims data using a study-specific common data model was customized for this study. We measured the yearly prevalence of biological drug users and the frequency of switches between originator and biosimilars for infliximab, etanercept, and adalimumab separately and stratified them by calendar year and region. We then calculated the cumulative number of users and person-years (PYs) of exposure to individual biological drugs approved for IMIDs. For a number of safety outcomes (e.g., severe acute respiratory syndrome coronavirus 2 [SARS-COV-2] infection), we conducted a sample power calculation to estimate the PYs of exposure required to investigate their association with individual biological drugs approved for IMIDs, considering different strengths of association. Results From a total underlying population of almost 50 million inhabitants from 13 Italian regions, we identified 143,602 (0.3%) biological drug users, with a cumulative exposure of 507,745 PYs during the entire follow-up. The mean age ± standard deviation of biological drug users was 49.3 ± 16.3, with a female-to-male ratio of 1.2. The age-adjusted yearly prevalence of biological drug users increased threefold from 0.7 per 1000 in 2010 to 2.1 per 1000 in 2019. Overall, we identified 40,996 users of biosimilars of tumor necrosis factor (TNF)-α inhibitors (i.e., etanercept, adalimumab, and infliximab) in the years 2015–2019. Of these, 46% (N = 18,845) switched at any time between originator and biosimilars or vice versa. To investigate a moderate association (incidence rate ratio 2) between biological drugs approved for IMIDs and safety events of interest, such as optic neuritis (lowest background incidence rate 10.4/100,000 PYs) or severe infection (highest background incidence rate 4312/100,000 PYs), a total of 43,311 PYs and 104 PYs of exposure to individual biological drugs, respectively, would be required. As such, using this network, of 15 individual biological drugs approved for IMIDs, the association with those adverse events could be investigated for four (27%) and 14 (93%), respectively. Conclusion The VALORE project multi-database network has access to data on more than 140,000 biological drug users (and > 0.5 million PYs) from 13 Italian regions during the years 2010–2019, which will be further expanded with the inclusion of data from other regions and more recent calendar years. Overall, the cumulated amount of person-time of exposure to biological drugs approved for IMIDs provides enough statistical power to investigate weak/moderate associations of almost all individual compounds and the most relevant safety outcomes. Moreover, this network may offer the opportunity to investigate the interchangeability of originator and biosimilars of several TNFα inhibitors in different therapeutic areas in real-world settings. Supplementary Information The online version contains supplementary material available at 10.1007/s40259-021-00498-3.

Published
2021

13. Diffuse malignant peritoneal mesothelioma: Evaluation of systemic chemotherapy with comprehensive treatment through the RENAPE Database: Multi-Institutional Retrospective Study

Author

Averous, G., Bereder, J.M., Bibeau, F., Bouzard, D., Chevallier, A., Croce, S., Dartigues, P., Durand-Fontanier, S., Gouthi, L., Heyd, B., Kaci, R., Kianmanesh, R., Laverrière, M.H., Leblanc, E., Lelong, B., Leroux, A., Loi, V., Mariette, C., Meeus, P., Msika, S., Pezet, D., Peyrat, P., Pirro, N., Paineau, J., Poizat, F., Porcheron, J., Quenet, F., Rat, P., Regimbeau, J.M., Thibaudeau, E., Tuech, J.J., Valmary-Degano, S., Verriele, V., Zerbib, P., Zinzindohoue, F., Kepenekian, V., Elias, D., Passot, G., Mery, E., Goere, D., Delroeux, D., Ferron, G., Guilloit, J.M., Pocard, M., Abboud, K., Arvieux, C., Brigand, C., Marchal, F., Classe, J.M., Lorimier, G., De Chaisemartin, C., Guyon, F., Mariani, P., Ortega-Deballon, P., Isaac, S., Maurice, C., Gilly, F.N., and Glehen, O.

Published
2016
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17. Potential histological discordance revealed by second review in the national rare gynecological cancer network (TMRG)

Author

Henno, S., primary, Jeanne, C., additional, Rouge, T. De La Motte, additional, Genestie, C., additional, Treilleux, I., additional, Croce, S., additional, Just, P.A., additional, Le Frere-Belda, M.A., additional, Guinaudeau, E., additional, Penault-Llorca, F., additional, Arnould, L., additional, Mery-Lamarche, E., additional, Leroux, A., additional, Lemaire, A.S., additional, Averous, G., additional, Renaud, O., additional, Charafe-Jauffret, E., additional, Bonneau, C., additional, Leaha, C., additional, Ray-Coquard, I., additional, and Devouassoux-Shisheboran, M., additional

Published
2022
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21. COVID-19 Vaccination in Pregnancy, Paediatrics, Immunocompromised Patients, and Persons with History of Allergy or Prior SARS-CoV-2 Infection: Overview of Current Recommendations and Pre- and Post-Marketing Evidence for Vaccine Efficacy and Safety

Author

Luxi N., Giovanazzi A., Capuano A., Crisafulli S., Cutroneo P. M., Fantini M. P., Ferrajolo C., Moretti U., Poluzzi E., Raschi E., Ravaldi C., Reno C., Tuccori M., Vannacci A., Zanoni G., Trifiro G., Petrelli G., Girotti S., Arzenton E., Magro L., Lora R., Bellantuono D., Sabaini A., Firenze A., Zodda D., Guidotti F., Zappone M., Alagna B., Spina E., Minore C., Costantino C., Conforto A., Vitale F., Morreale I., Marsala L., Farinella D., Bavetta S., Sapigni E., Potenza A. M., Podetti D., Nikitina V., Ricciardelli R., Mogheiseh N., Croce S., Paltrinieri B., Castellani S., Sangiorgi E., Selleri M., Lucchesi S., Catucci G., Savini D., Sacripanti C., Faccioli M., Romio M. S., Rossi L., Radici S., Negri G., Fares L., Ajolfi C., Fadda A., Chiarello A., Pieraccini F., Pappalardo F., Bonaiuti R., Lombardi N., Crescioli G., Tessari R., Zandona E., Marchiori F., Chiamulera C., Senna G., Crivellaro M. A., Cancian M., Venturini F., Ferri M., Leonardi L., Orzetti S., Caccin E., Baldo P., Rafaniello C., Pagliaro C., Mercaldo M., Fucile A., di Giorgio A., Tari M., Manna S., Farina G., Di Mauro C., De Carlo I., Senesi I., Pileggi C., Palleria C., Gallelli L., De Sarro G., Trabace L., Morgese M., Schiavone S., Tucci P., Bove M., Lapi F., Cricelli C., Racagni G., Tonolo S., Leopardi E., Fava G., Giuffrida S., Amato V., Gambera M., Montresor V., Luxi N., Giovanazzi A., Capuano A., Crisafulli S., Cutroneo P.M., Fantini M.P., Ferrajolo C., Moretti U., Poluzzi E., Raschi E., Ravaldi C., Reno C., Tuccori M., Vannacci A., Zanoni G., Trifiro G., Luxi, N., Giovanazzi, A., Capuano, A., Crisafulli, S., Cutroneo, P. M., Fantini, M. P., Ferrajolo, C., Moretti, U., Poluzzi, E., Raschi, E., Ravaldi, C., Reno, C., Tuccori, M., Vannacci, A., Zanoni, G., Trifiro, G., Petrelli G., Girotti S., Arzenton E., Magro L., Lora R., Bellantuono D., Sabaini A., Firenze A., Zodda D., Guidotti F., Zappone M., Alagna B., Spina E., Minore C., Costantino C., Conforto A., Vitale F., Morreale I., Marsala L., Farinella D., Bavetta S., Sapigni E., Potenza A.M., Podetti D., Nikitina V., Ricciardelli R., Mogheiseh N., Croce S., Paltrinieri B., Castellani S., Sangiorgi E., Selleri M., Lucchesi S., Catucci G., Savini D., Sacripanti C., Faccioli M., Romio M.S., Rossi L., Radici S., Negri G., Fares L., Ajolfi C., Fadda A., Chiarello A., Pieraccini F., Pappalardo F., Bonaiuti R., Lombardi N., Crescioli G., Tessari R., Zandona E., Marchiori F., Chiamulera C., Senna G., Crivellaro M.A., Cancian M., Venturini F., Ferri M., Leonardi L., Orzetti S., Caccin E., Baldo P., Rafaniello C., Pagliaro C., Mercaldo M., Fucile A., di Giorgio A., Tari M., Manna S., Farina G., Di Mauro C., De Carlo I., Senesi I., Pileggi C., Palleria C., Gallelli L., De Sarro G., Trabace L., Morgese M., Schiavone S., Tucci P., Bove M., Lapi F., Cricelli C., Racagni G., Tonolo S., Leopardi E., Fava G., Giuffrida S., Amato V., Gambera M., and Montresor V.

Subjects
Allergy, IMPACT, COVID-19 Vaccine, Breastfeeding, Review Article, Toxicology, Settore MED/42 - Igiene Generale E Applicata, CLINICAL CHARACTERISTICS, Pregnancy, Pharmacology (medical), Pregnancy Complications, Infectious, Child, OUTCOMES, education.field_of_study, CANCER, Vaccination, Europe, CORONAVIRUS DISEASE 2019, CLINICAL CHARACTERISTICS, CANCER, RECIPIENTS, SEVERITY, OUTCOMES, IMPACT, RATES, Breast Feeding, Child, Preschool, Practice Guidelines as Topic, Female, 2019-nCoV Vaccine mRNA-1273, Human, Adult, medicine.medical_specialty, COVID-19 Vaccines, Adolescent, BNT162 Vaccine, COVID-19, ChAdOx1 nCoV-19, Humans, Infant, SARS-CoV-2, Hypersensitivity, Immunocompromised Host, Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), Population, MEDLINE, CORONAVIRUS DISEASE 2019, medicine, RATES, education, Pharmacology, business.industry, medicine.disease, Vaccine efficacy, RECIPIENTS, SEVERITY, Family medicine, Pregnancy Complications, Infectiou, business
Abstract

To date, four vaccines have been authorised for emergency use and under conditional approval by the European Medicines Agency to prevent COVID-19: Comirnaty, COVID-19 Vaccine Janssen, Spikevax (previously COVID-19 Vaccine Moderna) and Vaxzevria (previously COVID-19 Vaccine AstraZeneca). Although the benefit–risk profile of these vaccines was proven to be largely favourable in the general population, evidence in special cohorts initially excluded from the pivotal trials, such as pregnant and breastfeeding women, children/adolescents, immunocompromised people and persons with a history of allergy or previous SARS-CoV-2 infection, is still limited. In this narrative review, we critically overview pre- and post-marketing evidence on the potential benefits and risks of marketed COVID-19 vaccines in the above-mentioned special cohorts. In addition, we summarise the recommendations of the scientific societies and regulatory agencies about COVID-19 primary prevention in the same vaccinee categories. Supplementary Information The online version contains supplementary material available at 10.1007/s40264-021-01131-6.

Published
2021

22. EA Wind TCP Task 29, Phase IV: Detailed Aerodynamics of Wind Turbines

Author

Schepers, Gerard, Boorsma, Koen, Madsen, H.A., Pirrung, G.R., Bangga, G., Guma, Giorgia, Lutz, Thorsten, Potentier, Thomas, BRAUD, Caroline, Guilmineau, Emmanuel, u, A. Croce, S. Cacciola, A. P. Scha arczyk, B. A. Lobo, S. Ivanell, H. Asmuth, F. Bertagnolio, N.N. Srensen, W. Z. Shen, C. Grinderslev, A. M. Forsting, F. Blondel, P. Bozonnet, R. Boisard, K. Yassin, L. Honing, B. Stoevesandt, M. Imiela, L. Greco, C. Testa, F. Magionesi, G. Vijayakumar, S. Ananthan, M. A. Sprague, E. Branlard, J. Jonkman, M. Carrion, S. Parkinson, E. Cicirel, The Netherlands Organisation for Applied Scientific Research (TNO), Danmarks Tekniske Universitet (DTU), Universität Stuttgart [Stuttgart], ON TE PD5X LACS LC LOADS Department, Siemens Gamesa Renewable Energy (RDT Engineers), 7330 Brande, Denmark, Laboratoire de recherche en Hydrodynamique, Énergétique et Environnement Atmosphérique (LHEEA), École Centrale de Nantes (ECN)-Centre National de la Recherche Scientifique (CNRS), Engie-Green - Nantes, and Centre Scientifique et Technique du Bâtiment (CSTB)

Subjects
[SPI.FLUID]Engineering Sciences [physics]/Reactive fluid environment
Abstract

International audience; This report describes the final results of the fourth phase of IEA TCP Wind Task 29. The project period of this fourth phase was from January 1 st 2018 until December 31 st 2020. It was the follow-up of three former IEA Task 29 phases (often denoted as Mexnext-I to Mexnext-III). In all phases wind turbine aerodynamic models were validated and improved with detailed aerodynamic measurements. In these detailed aerodynamic experiments pressure distributions at different locations along the rotor blades are measured anyhow where measurements of e.g. inflow velocities and boundary layer transition are very nice to know. The first three phases were mainly built around wind tunnel measurements on a small scale wind turbine with rotor diameter of 4.5 meter from the (New) Mexico project but the present phase was built around field measurements from the DanAero experiment.This DanAero experiment was carried out at atmospheric field conditions on a 2MW turbine by Danish Technical University DTU and 4 industrial partners (LM Glassfiber, Siemens WindPower, Vestas and Dong Energy) in 2 periods from 2007 until 2010 and from 2010 until 2013. Amongst others surface pressures and inflow velocities were measured at four sections along a blade and a row of surface flush mounted microphones was installed at the outer part ofthe blade. In IEA Task29 Phase IV the DanAero data were made available to the IEA Task 29 participants which enabled a detailed analysis in a collaborative action. Amongst others a critical scrutinising of data took place with subsequent further improvement of measurement quality. Moreover the measurements were used as validation material for the many design models which are available in the consortium. A wide variety of models could be considered ranging from high fidelity (but time consuming) CFD to lower fidelity but efficient engineering models. Intermediate methods (e.g. free wake methods) were applied as well. Several calculational rounds were carried out where calculations were compared with measurements. Amongst others a case was defined at simple steady and axi-symmetric conditions close to a measurement case with little shear and little yaw but also measurement cases at high yaw and high shear were simulated. Moreover the level of detail from the DanAero experiment allowed an in-depth analysis of several wind turbine aerodynamic aspects, e.g. Aerodynamic response to turbulent inflow; Sheared inflow; 2D/3D aerodynamics;Aeroelastic effectsTransition characteristics in realistic flow conditions;Acoustics. The project was carried out by a consortium which consisted of research groups and industries from 9 different countries China: Chinese Wind Energy Association, CWEA Denmark: Technical University of Denmark, DTU, Siemens-Gamesa Renewable Energy France: IFPEn, LHEEA lab - Centrale Nantes/CNRS, ONERA, EDFGermany: ForWind/Fraunhofer IWES, Kiel University of Applied Sciences, University of Stuttgart, WindNovation, Enercon Deutsches Zentrum für Luft- und Raumfahrt e.V., DLR University of Applied Sciences EmdenItaly: PoliMi, RSE, CNR - INMNetherlands: TNO Energy Transition (formerly ECN, Operating Agent), Delft University of Technology, TUDelft, DNV-GL Suzlon Blade Technology, SBT, CWI, LM and University of Twente, UTwenteItaly: PoliMi, RSE, CNR - INMSweden: Uppsala University, Campus GotlandSwitzerland: UAS RapperswilUSA: National Renewable Energy Laboratory, NREL

Published
2021

26. Application of stem cells in oral science: a literature review

Author

Lucchese A., Botta R., Lucchese C., Croce S., Marcolina M., Manuelli M., Lucchese, A., Botta, R., Lucchese, C., Croce, S., Marcolina, M., and Manuelli, M.

Subjects
Mouth, Stem cell, Regenerative dentistry, Stem Cells, Humans, Tissue engineering
Abstract

The objective of this work was to provide a review of the literature on studies of stem cells and their potential applications in dental practice. Research included every article published between 2000 and 2018 in PubMed PMC, Scopus, Cochrane Trial Library, and Web of Science databases featuring the keywords: regenerative dentistry, stem cells, tissue engineering. Papers that did not directly address the subject were excluded. Emphasis was given to scientific studies that showed possibilities of stem cell therapy in the oral and maxillofacial region. The methodological quality of selected papers was scored using the “Swedish Council on Technology Assessment in Health Care Criteria for Grading Assessed Studies” (SBU) method. Two review authors independently assessed eligibility, extracted data and verified the quality of the studies.

Published
2019

29. Arcagen: Molecular profiling of rare cancer patients – analysis of the pilot study (87 patients)

Author

Morfouace, M., primary, Ray-Coquard, I., additional, Girard, N., additional, Stevovic, A., additional, Treilleux, I., additional, Meeus, P., additional, Aust, S., additional, Floquet, A., additional, Croce, S., additional, Seckl, M., additional, Gietema, J., additional, Caplin, M., additional, delaFouchardiere, C., additional, Licitra, L., additional, Kapiteijn, H., additional, Neumann, S. Piperno, additional, Idbaih, A., additional, and Blay, J.Y., additional

Published
2020
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30. LBA67 TRAMUNE, a phase Ib study combining trabectedin and durvalumab, results of the expansion cohort in patients with advanced pretreated soft tissue sarcomas

Author

Toulmonde, M., primary, Brahmi, M., additional, Giraud, A., additional, Bessede, A., additional, Kind, M., additional, Toulza, E., additional, Pulido, M., additional, Cousin, S., additional, Bourcier, K., additional, Albert, S., additional, Mothes, S., additional, Chakiba, C., additional, Ray-Coquard, I.L., additional, Floquet, A., additional, Croce, S., additional, Mathoulin-Pélissier, S., additional, Perret, R., additional, Blay, J-Y., additional, and Italiano, A., additional

Published
2020
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31. Early and late outcome of treated patients referred for syncope to emergency department: the EGSYS 2 follow-up study

Author

Ungar, Andrea, Del Rosso, Attilio, Giada, Franco, Bartoletti, Angelo, Furlan, Raffaello, Quartieri, Fabio, Lagi, Alfonso, Morrione, Alessandro, Mussi, Chiara, Lunati, Maurizio, De Marchi, Giuseppe, De Santo, Tiziana, Marchionni, Niccolò, Brignole, Michele, Ammirati, F, Brignole, M, Casagranda, I, Cortelli, P, Disertori, M, Furlan, R, Giada, F, Iori, I, Lagi, A, Lunati, M, Mathieu, G, Menozzi, C, Miceli, G, Mussi, C, Ponzi, P, Raviele, A, Re, G, Ribani, MA, Sandrone, G, Scivales, A, Ungar, A, Alessandria, SS., De Marchi, PG, Casagranda, I, Bologna, Marenco M., Orsola Malpigli e Belluria, Policlinico S., Re, G, Como, Ribani MA., Crema, Foglia Manzillo, Cuneo, Durin O., Croce, S., Vado, A, Firenze, Poggi A., Bartoletti, A, Bagnoli, L, Firenze, Fabiani P., Maria, S., Firenze, Lagi A, Ungar, A, Fucecchio, Masotti G., Pietro Del, S., Garbagnate, Rosso A., Genova, Dassi S., Martino, Azienda Ospedaliera, Ponassi, I, Lavagna, Baldi G., del Tigullio, Ospedali, Brignole, M, Maggi, R, Mestre, Saggese PM., Umberto, I, Giada, F, Milano, Raviele A., Sacco, Azienda Ospedaliera, Furlan, R, Milano, Borella M., Lunati, M, Vecchi, R, Modena, Vicari F., Mussi, C, Reggio Emilia, Salvioli G., Maria Nuova, Arcispedale S., Menozzi, C, Rho, Quartieri F., Rovelli, G, Trento, Ferrari F., Tava, G, and Del Greco, M.

Published
2010
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34. Agenesis: pilot case report by 2.9 mm implant

Author

Zanotti, G, Gelpi, F, Sinigaglia, S, Croce, S, Tacchino, U, Perozeni, G, Luciano, U, and De Santis, D

Subjects
Incisor, Male, agenesis, implant surgery, aesthetic rehabilitation, Gingiva, Maxilla, Humans, Middle Aged, Anodontia
Abstract

The agenesis of the upper lateral incisor is one of the most frequent aesthetic-functional problems in dentistry. The reported case concerns a 49 years old male patient with bilateral agenesis of teeth 1.2-2.2 and a root stump of tooth 5.2 temporarily rehabilitated through a Maryland bridge. Without orthodontic treatment, the only solution for implant-prosthetic rehabilitation of tooth 1.2 results therefore in the use of a 2.9 mm diameter implant. The clinical and radiographic control of the implant and the gingival stability at a distance of 1 year gives a positive result both clinically and radiographically. The use of the implant with a 2.9 mm diameter is therefore indicated in extreme cases of limited bone availability.

Published
2019

43. Analysis of the Genomic Profile in Disseminated Peritoneal Leiomyomatosis: Three cases

Author

Cavillon, Bruno Langer, Averous, Viviani, Nicolas Sananès, J.J. Baldauf, Cherif Akladios, E. Boudier, and Croce S

Subjects
Pathology, medicine.medical_specialty, 030219 obstetrics & reproductive medicine, Lineage (genetic), business.industry, Pathogenesis, 03 medical and health sciences, Peritoneal cavity, 0302 clinical medicine, medicine.anatomical_structure, 030220 oncology & carcinogenesis, Genomic Profile, medicine, business, Exome, Disseminated Peritoneal Leiomyomatosis, Rare disease, Comparative genomic hybridization
Abstract

Disseminated peritoneal leiomyomatosis (DPL) is a rare disease entity belonging to the category of smooth muscle tumours of uncertain growth. It is characterized by proliferation of multiple smooth muscle nodules in the peritoneal cavity mimicking a malignant process such as peritoneal carcinomatosis but which when studied histologically proves to be of benign nature. Its origin is still unknown. Genomic analysis of DPL cases is of interest in order to understand its pathogenesis and subsequent course, but there are few extant studies. In this article we set out the genomic profiles, analysed by array-based comparative genomic hybridization (array-CGH), of peritoneal and uterine lesions in two cases of DPL detected after previous uterine morcellation for fibroids, as well as a "sporadic" case of DPL. Array-CGH findings revealed in all three cases a flat genomic profile. It is not possible to establish a genetic lineage between two lesions on the basis of the genomic profiles alone, owing to the absence of an unbalanced rearrangement. CGH is not conclusive enough in this type of disorder. Analysis of the exome could provide us with fresh information, not least about driving events in the cancerogenesis of these tumours.

Published
2017

47. Mucinous Neoplasms Of The Appendix And Peritoneum: Virtual Microscopy For Histomorphologic Assessment And Interobserver Diagnostic Reproducibility : SY02.06 | Telepathology

Author

Villa, I., Villeneuve, L., Carr, N. J., Isaac, S., Glehen, O., Capovilla, M., Chevallier, A., Croce, S., Kaci, R., Lang-Averous, G., Laverriere, M.-H., Leroux-Broussier, A., Mery, E., Poizat, F., Valmary-Degano, S., Verriele-Beurrier, V., Gilly, F.-N., Bibeau, F., and Dartigues, P.

Abstract

INTRODUCTION / BACKGROUND: Among gastrointestinal (GI) tumours, pseudomyxoma peritonei (PMP) from appendiceal origin has unique clinical and morphologic features. Due to the relative paucity of patients and the absence of therapeutic consensus, evaluation and refinement of the morphologic criteria used for assessment of the disease are still difficult. As a result, a uniformly accepted classification is still lacking. In collaboration with NJ Carr, who initiated the conference consensus process, in Basingstoke, and on behalf of the French group RENA-PATH, 11 experienced GI pathologists agreed to participate to a virtual workshop, in order to assess inter-observer variability in PMP diagnosis and staging. AIMS: The goal of the study was to evaluate, for appendiceal and peritoneal mucinous neoplasms, the degree of concordance in the identification of diagnostic histological criteria by experienced pathologists, and to assess the degree of inter-individual variation in the application of WHO classification (2010) and TNM staging system (7th edition). METHODS: A single section stained with hematoxylin and eosin from 9 resected cases of mucinous neoplasms was selected by members of RENA-PATH. All digitalized at a maximum resolution (X40) using an HAMMAMATSU scanner system, to ensure that all participants evaluate exactly the same tumour areas; 1 to 16 questions were prepared for each case. On Teleslide web platform, interactive services provided by TRIBVN. All submitted cases were then reviewed by a panel of 11 pathologists with specific expertise and interest in PMP. Data were analyzed using SAS program. RESULTS: Whole slide set evaluated by all participants; no abstention or “unknown diagnosis” for any submitted case. Agreement for classification, WHO 2010: -Appendiceal mucinous neoplasms: LAMN 83 %; mucinous adenocarcinoma 92%. -Peritonei mucinous carcinoma: Low grade 91.7%; high grade 91.7%. -Disagreement on the concept of High Grade AMN defined by low power architecture of LAMN + high grade cytology. -Agreement for using pTNM classification (82%) in PMP. -Pushing Invasion (PI) and dissection by acellular mucin (DAM) in appendix wall are not reproducible criteria and need to be better defined. -Criteria need to be redefined to use HAMN according to a majority of participants. -The identification of signet ring cells is not reproducible; the lesion needs to be better defined. -Invasion of organs and pattern of invasion (broatfront invasion / classic by irregular glands or single cells with desmoplasia) are not reproducible criteria. -Improvement in staging assessment is needed

Published
2016

49. P003 Implementation of High Throughput Parallel Sequencing in a Diagnostic Setting: Multiplexed Amplicon Sequencing of the Breast Cancer Genes BRCA1 and 2

Author

Zogopoulos G, Tomi Pastinen, Sivanandan K, Vaca F, Kinoshita T, Johannes B, Leguis E, Jansen-van der Weide M, Learn L, Godlewski D, Ed Saunders, Montserrat Rué, Vaisman A, de Bock G, Ángel Segura, Sabbaghian N, Mohammad Amin Kerachian, Pelletier S, Metcalfe K, Lilge L, Stockle E, Cheng S, Burger C, Woike A, Michelle Guy, Ragone A, Y. J. Bignon, Bronkhorst Y, Patricia N. Tonin, Lima M, Mieke Kriege, Karsan A, Zweemer R, Prady C, Beattie M, Panchal S, Kathleen Claes, van Zon P, Diane Provencher, Ummels A, Kang I, Shumak R, Arcusa Â, Yosr Hamdi, Alonso Mc, Dolman L, Houssami N, Olivier Delattre, Yannick Bidet, Claude Houdayer, Mercedes Durán, Ganschow P, Isabel Chirivella, Domingo S, Rebsamen M, Giustina Simone, Orland Diez, Chapman J, An tSaoir C, Jeanna McCuaig, Blayney J, Bosdet I, Treacy R, Esther Darder, Ando J, Luc Dehaspe, García-Casado Z, Duffy J, Harkin D, Z Kote-Jarai, Kasamatsu T, Ulf Kristoffersson, Membrez, Priston M, Noreau-Heisz D, Trivedi A, Begoña Graña, Ghadirian P, Ashuryk O, Consol López, Wenzel L, Vogel R, Joseph G, Poll A, Kennedy R, Patton S, Pérez C, Mónica Cornet, Panighetti A, Cassart P, Burke K, Mes-Masson A, Llacuachaqui M, Marc Tischkowitz, Wong N, Arcand S, Kotsopoulos J, Meschino W, Hall A, Marles S, Docking R, Haroun I, Marie Plante, Rachel Laframboise, Daniel Sinnett, Luce J, Sekiguchi I, Edenir Inêz Palmero, de Winter J, Christopher J. Lord, Hamel N, Pruski-Clark J, Lee D, Rusnak A, Carson N, Marta Santamariña, Knoppers B, Oakhill K, Bruce R. Rosen, Pierre O. Chappuis, Bruce Poppe, Stanislaw C, Catts Z, Brood M, van der Wall E, Yip C, Christine Walsh, Hoodfar E, Pressman A, Andrulis I, Alicia Barroso, D. Leongamornlert, Gillian Mitchell, Akira Hirasawa, Shen Z, Sameer Parpia, Horgan M, van Echtelt J, Chun K, Lubinski J, Rebecca Sutphen, Terespolsky D, Richard D, McDyer F, Floquet A, Lambo R, Bathurst L, Brown G, Kidd M, Nicolas Sevenet, Mourits M, Vencken P, Tatiana Popova, Garcia N, Armel S, van Amstel H, Valentini A, Ellen Warner, Hofland N, Hanna D, Kim J, Osann K, Enmore M, Loranger K, Sulivan I, J. Oliveira, Meijers H, Jansen R, Edmundo Carvalho Mauad, Kirkpatrick R, Danilo V Viana, Ian G. Campbell, Mil S, E J Sawyer, J. Balmaña, Samra Turajlic, Graham G, Alonso C, Inanc Birol, Sinclair F, van Tuil M, Pascual Bolufer, Micheli R, Andrew R. Green, Junyent N, Whittaker J, Monnerat C, Rhéaume J, Livingston D, Chan S, L. Ramadan, Lee R, Katarzyna Durda, De Leeneer K, Grados C, Côté C, Kyle B. Matchett, Robert Winqvist, Bonner D, Brunella Pilato, Mohd Taib N, Judy Garber, Kleiderman E, Murakami S, Sharifi N, Kimberley Hill, Desbiens C, Robert Royer, Jasperson K, Hsieh S, De Summa S, Dominique Stoppa-Lyonnet, de Lima J, Stuart McIntosh, Shakeri M, Wendy Kohlmann, Albert-Green A, de Hullu J, Pasick R, Avard D, Pathania S, van der Groep P, Laura Fachal, Bruno Zeitouni, Susan M. Domchek, Davey S, Richard Marais, Powell C, Hans J. J. P. Gille, Greenberg R, Kamata H, Cina, Gaarenstroom K, Lakhal Chaieb M, Kavanagh L, Gaelle Benais-Pont, Sun P, Jansen L, Matthew Parker, Barjhoux L, Russ H, Simon J. Furney, Willems A, Robb L, David E. Goldgar, Young S, Natalia Campacci, Mark G. Thomas, Doug Easton, Klugman S, Barrault M, Calvo N, Adriana C. Flora, Littell R, Narod S, Fragoso, N. Bosch, Finch A, Paul M. Wilkerson, Teo S, Tomasz Huzarski, Manuel Salto-Tellez, Moseley M, Davis S, Olga M. Sinilnikova, Iturbe A, Joan Brunet, Tierney M, Tsai E, Navarro de Souza A, Leclerc M, Lorenzo Manti, Gutiérrez-Enríquez S, Milewski B, Simon S. McDade, Kaplan C, Buckley N, Eva Esteban-Cardeñosa, Richter S, Shimizu C, Li J, Elena Castro, Iwanka Kozarewa, Harley I, Atocha Romero, Carlos E. Andrade, Carole Verny-Pierre, Barouk E, Vian D, Montserrat Baiget, Chan J, Sandra Bonache, Andrew Y Shuen, van der Merwe N, Kaklewski K, Mohar A, Tamura C, Heale E, Rooyadeh M, van Asperen C, Gemma Llort, Alan Mackay, Denroche R, Seelaus C, Zbuk K, McCluggage W, van der Luijt R, Maaike P.G. Vreeswijk, Edelweiss M, Crossan G, Arseneau J, Ambus I, Verheul H, Rodrigo Augusto Depieri Michelli, Juul T. Wijnen, Gross-Lester J, Britta Weigelt, Pedro Pérez-Segura, Richard A. Moore, Cornelissen C, Larouche G, McAlpine J, Daniel Nava Rodrigues, Trim L, Furnival J, Elser C, Muszyńka M, Adriana Lasa, Tuya Pal, Greuter. M, Ng K, Dorval M, Bresee C, Reimnitz G, Gaëtan MacGrogan, Perry Maxwell, Barnadas A, Hwang E, Powell B, Knapke S, Griskevicius. L, Alvarez R, Mester J, Anne-Bine Skytte, Eladio Velasco, Vidal S, Australie K, Leunen K, Ben-Yishay M, Van Houdt J, Phuah S, Amy E Taylor, Pinto R, Fonseca T, Champine M, Gammon A, Hollema H, Menko F, Feng B, David Olmos, Chong G, Tomasz Byrski, Patrick J. Morrison, Gregoire J, André Lopes Carvalho, Don B. Plewes, Rabeneck L, Carrol J, Alan Ashworth, Terlinge A, A Jakubowska, Odette Mariani, Setareh Moghadasi, Reitsma W, Rothenmund H, Herrera L, Anna Tenés, Angel Izquierdo, Asunción Torres, Stawicka M, Goh C, Hirst M, Drummond J, Osorio A, Ostrovsky R, Jeffrey N. Weitzel, Gareth W. Irwin, Fehniger J, Sugano K, Spriggs E, Dęniak T, Volenik A, Thorne H, Piccinin C, Amie Blanco, Jinno H, Robert A. Holt, Stephen B. Fox, Julia J. Gorski, Gilpin C, Herschorn S, Vega A, E. Page, Hamet P, McKenna D, Fabrice Bonnet, Yoshida T, Kienan I. Savage, Petzel S, Elizabeth Bancroft, Schneider S, Warwick L, Stewart S, William D. Foulkes, Colizza K, Bell K, Demsky R, Malgorzata Tymrakiewicz, Caldés T, Fons G, Bowen D, Côté S, Clouston D, Kitagawa Y, Gordon Glendon, Jenny Lester, Kinney A, Nelson E, Silke Hollants, Macrae L, Cajal T, Andrew J. Mungall, Ferrell B, Creighton B, Bressler L, Uy P, Makishima K, Haffaf Z, Ramūnas Janavičius, Einstein G, Zakalik D, Chiarelli A, Cantu D, Croce S, Kalloger S, Lin F, Ian O. Ellis, Benedito Mauro Rossi, R A Wilkinson, Mulligan J, Murphy J, Vadaparampil S, Smith E, Slangen B, Loiselle C, Iqbal J, Palma L, Cooper K, Jorge S. Reis-Filho, Chen. L, Quinten Waisfisz, Haneda E, Banks P, Vermeulen K, Visser B, Montalbán G, McCabe N, Honeyford J, Naseri S, Ng J, Ali A, Sandrine Viala, Mensa I, Kamarainen O, Guerra C, Mazzola E, David A. Schwartz, Marjanka K. Schmidt, Simon R, Fergus J. Couch, Margreet G. E. M. Ausems, Anne Vincent-Salomon, Olinski R, Zewald R, Moreno R, Semple J, McPherson J, Lamers E, Kharbanda A, Kessler L, Biemans D, Au A, Bordeleau L, Jean Feunteun, Mar Infante, Mullan P, Rudaitis, Molenda A, Rachael Natrajan, Pawar, Boman B, Kok T, Andrew A. Brown, Geller M, Monfared N, Bart J, Murata P, Crawford N, Butterfield Y, Bargalló J, Katherine L. Tucker, Cook-Wiens G, Rhodes A, Elodie Manié, Rubio E, Oram L, Shandiz F, Hayden R, Crawford B, Parmigiani G, Harkin P, Müller C, Grant M, Maryou B. Lambros, Thong M, Grzegorz Sukiennicki, Wouts J, Haddock P, Ramon y Cajal T, Kenneth C. Anderson, Michel Longy, Batiste W, Carroll J, Matte C, Hojyo T, Zhao Y, Caroline Seynaeve, Wai P, Simard J, Hurley K, Bolton D, Karlan B, Javier Benítez, Miriam Masas, Tołczko-Grabarek A, de Dueñas E, Geneviève Michils, Moncoutier, Nancy Uhrhammer, MacDonald D, Keyserlingk J, Osher D, Gilks C, Christopher T. Elliott, Scharf L, Gabram-Mendola S, Grondin K, Dohany L, van Diest P, Joris Vermeesch, Jan C. Oosterwijk, M’Baïlara K, DePuit M, Jacek Gronwald, Stefania Tommasi, de la Hoya M, Bouchard K, Black L, Lui M, Soucy P, Rosalind A. Eeles, Gert Matthijs, Graham T, Andrea Eisen, Bacha O, Alvaro N.A. Monteiro, Yoon S, Caron T, Smith D, Marc-Henri Stern, Hampson E, Kurz R, Gaasbeek W, Mundt E, Angela Velasco, Quinn J, Jocelyne Chiquette, Marquez T, Adam B. Murphy, Bakker J, Neus Gadea, Anita Grigoriadis, Aoki D, Dean S, Looi L, Paradiso A, Agostina Stradella, K. Govindasami, Lovell N, Eva Tomiak, Siesling S, Belanger M, Feilotter H, Knight J, Emmanuel Barillot, Huang M, Raquel Andrés, Kang P, Somerman C, Gackowski D, Rimel B, Nakamura S, McClellan K, Barrros E, Henriette Roed Nielsen, Rui Manuel Reis, Greening S, Ayme A, Carmen Guillen, de Vries E, and Katarzyna Jaworska

Subjects
Oncology, Education and Communication, medicine.medical_specialty, endocrine system diseases, medicine.diagnostic_test, business.industry, Psycho-Oncology, medicine.disease, Meeting Abstracts, Transcriptome, Basic Research, Clinical Management, Germline mutation, Breast cancer, Applied Research, Internal medicine, Mutation (genetic algorithm), medicine, Genetic Counselling, Human genome, skin and connective tissue diseases, business, Ovarian cancer, Comparative genomic hybridization, Fluorescence in situ hybridization
Abstract

Background: Germline mutation screening of BRCA1 and BRCA2 genes is performed in suspected familial breast cancer cases, but a causative mutation is found in only 30% of patients. The development of additional methods to identify good candidates for BRCA1 and BRCA2 analysis would therefore increase the efficacy of diagnostic mutation screening. With this in mind, we developed a study to determine molecular signatures of BRCA1—or BRCA2—mutated breast cancers. Materials and Methods: Array-cgh (comparative genomic hybridization) and transcriptomic analysis were performed on a series of 103 familial breast cancers. The series included 7 breast cancers with a BRCA1 mutation and 5 breast cancers with a BRCA2 mutation. The remaining 91 cases were obtained from 73 families selected on the basis of at least 3 affected first-degree relatives or at least 2 affected first-degree relatives with breast cancer at an average age of 45 years. Array-cgh analyses were performed on a 4407 BAC-array (CIT-V8) manufactured by IntegraGen. Transcriptomic analyses were performed using an Affymetrix Human Genome U133 Plus 2.0 chip. Results: Using supervised clustering analyses we identified two transcriptomic signatures: one for BRCA1-mutated breast cancers consisting of 600 probe sets and another for BRCA2-mutated breast cancers also consisting of 600 probes sets. We also defined cgh-array signatures, based on the presence of specific genomic rearrangements, one for BRCA1-mutated breast cancers and one for BRCA2-mutated breast cancers. Conclusions: This study identified molecular signatures of breast cancers with BRCA1 or BRCA2 germline mutations. Genes present in these signatures could be exploited to find new markers for such breast cancers. We also identified specific genomic rearrangements in these breast cancers, which could be screened for in a diagnostic setting using fluorescence in situ hybridization, thus improving patient selection for BRCA1 and BRCA2 molecular genetic analysis.

Published
2009

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