117 results on '"Vicario R"'
Search Results
2. A dynamic modelling approach to manage the cruise port of call
- Author
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Fernández-Gámez, M.A., Valcarce-Ruiz, L., Becerra-Vicario, R., and Diéguez-Soto, J.
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- 2022
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3. A Methodology for Benchmarking Force Control Algorithms
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Vicario, R., primary, Calanca, A., additional, Murr, N., additional, Meneghetti, M., additional, Sartori, E., additional, Zanni, G., additional, and Fiorini, P., additional
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- 2021
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4. Dimensional and form errors of PC parts printed via Fused Deposition Modelling
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Reyes-Rodríguez, A., Dorado-Vicente, R., and Mayor-Vicario, R.
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- 2017
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5. Using IOTA terminology to evaluate fetal ovarian cysts: analysis of 51 cysts over 10‐year period
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Romiti, A., primary, Moro, F., additional, Ricci, L., additional, Codeca, C., additional, Pozzati, F., additional, Viggiano, M., additional, Vicario, R., additional, Fabietti, I., additional, Scambia, G., additional, Bagolan, P., additional, Testa, A. C., additional, and Caforio, L., additional
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- 2023
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6. Genetic insight in vein of Galen aneurysmal malformation
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Ronci, S., primary, Campi, F., additional, Longo, D., additional, Giliberti, P., additional, Pisaneschi, E., additional, Lozzi, S., additional, Caoci, S., additional, Pugnaloni, F., additional, Calì, M., additional, Di Pede, A., additional, Capolupo, I., additional, Vicario, R., additional, Digilio, M.C., additional, Novelli, A., additional, Dotta, A., additional, Gandolfo, C., additional, and Bagolan, P., additional
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- 2023
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7. Prevalence of Maternal Psychological Distress in pregnant women who receipt prenatal diagnosis of fetal Central Nervous System (CNS) anomalies
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Falamesca, C., primary, Cappelletti, S., additional, Vicario, R., additional, Amante, P.G., additional, Correale, C., additional, Vigevano, F., additional, Caforio, L., additional, and Grimaldi Capitello, T., additional
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- 2022
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8. Transperineal robotic prostate biopsy with prost: a pilot study
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Iseppi, A., primary, Puliatti, S., additional, Ferrari, R., additional, Piro, A., additional, Amato, M., additional, Sighinolfi, M.C., additional, Rizzo, M., additional, Maris, B., additional, Tenga, C., additional, Vicario, R., additional, Calanca, A., additional, Fiorini, P., additional, Bianchi, G., additional, Rocco, B., additional, and Micali, S., additional
- Published
- 2021
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9. The asymptomatic, high-grade refluxing male. ciinical follow up of a new cohort of patients derived from prenatal diagnosis
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Zaccara, A., primary, Lais, A., additional, Capitanucci, M.L., additional, Mosiello, G., additional, Silveri, M., additional, Vicario, R., additional, Romiti, A., additional, Viggiano, M., additional, and Caforio, L., additional
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- 2020
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10. VP15.07: Physiological changes in cardiac dimensions and function in low‐risk pregnancies
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Viggiano, M., primary, Vassallo, C., additional, Massolo, A., additional, Vicario, R., additional, Romiti, A., additional, Bagolan, P., additional, and Caforio, L., additional
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- 2020
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11. Hypersensitivity pneumonitis induced by exposure to the legume algarroba
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Franco-Vicario, R., Gamboa, P., Escalante, M., Pueyo, V., Sanz, M. L., Solano, D., and Miguel, F.
- Published
- 1997
12. SC218 - Transperineal robotic prostate biopsy with prost: a pilot study
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Iseppi, A., Puliatti, S., Ferrari, R., Piro, A., Amato, M., Sighinolfi, M.C., Rizzo, M., Maris, B., Tenga, C., Vicario, R., Calanca, A., Fiorini, P., Bianchi, G., Rocco, B., and Micali, S.
- Published
- 2021
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13. SC344 - The asymptomatic, high-grade refluxing male. ciinical follow up of a new cohort of patients derived from prenatal diagnosis
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Zaccara, A., Lais, A., Capitanucci, M.L., Mosiello, G., Silveri, M., Vicario, R., Romiti, A., Viggiano, M., and Caforio, L.
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- 2020
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14. Accuracy of Three-Dimensional Saline Infusion Sonohysterography (3D-SIS) for Evaluation of Uterine Cavity Abnormalities in Infertility Patients
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Rouleau, JP, primary, Rodriguez Fuentes, A, additional, Pirollo, L, additional, Vicario, R, additional, Costa, M, additional, Hernandez, J, additional, Garcia Guzman, R, additional, and Palumbo, A, additional
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- 2016
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15. Hysteroscopic Polypectomy on the Day of Egg Retrieval, 5 Days Prior to Embryo Transfer: A Case Report
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García-Guzmán, R, primary, Rouleau, JP, additional, Hernández, J, additional, Vicario, R, additional, Pirollo, L, additional, and Palumbo, A, additional
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- 2016
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16. A propósito de un caso sobre tuberculosis miliar en paciente con tratamiento inmunosupresor
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Franco-Vicario, R., Llamazares-Medrano, J.M., Miguel-de-la-Villa, F., and Ucar-Angulo, E.
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- 2005
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17. Effect of Cellular Senescence on the Growth of HER2-Positive Breast Cancers
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Zacarias-Fluck, M. F., primary, Morancho, B., additional, Vicario, R., additional, Luque Garcia, A., additional, Escorihuela, M., additional, Villanueva, J., additional, Rubio, I. T., additional, and Arribas, J., additional
- Published
- 2015
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18. 306: Chemotherapy sensitizes p95HER2-positive breast cancers to trastuzumab
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Morancho, B., primary, Parra-Palau, J.L., additional, Peg, V., additional, Vicario, R., additional, Zacarias-Fluck, M., additional, Pedersen, K., additional, Perou, C.M., additional, Prat, A., additional, Rubio, I.T., additional, and Arribas, J., additional
- Published
- 2014
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19. 303: A role for senescent cell-derived IL6 in HER2+ breast cancer progression
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Zacarias Fluck, M., primary, Morancho, B., additional, Angelini, P.D., additional, Vicario, R., additional, Villarreal, L., additional, Aura, C., additional, Nuciforo, P., additional, Villanueva, J., additional, Rubio, I.T., additional, and Arribas, J., additional
- Published
- 2014
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20. New Software for Valutation of Uterine Septum
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Marziali, M, Pedone, M, and Vicario, R
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- 2016
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21. Nutrición, enfermedad ósea y cirrosis alcohólica
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Escalante Boleas, M. A., Franco Vicario, R., Cubas Largacha, L., Goiría Ormazábal, J. I., Zulueta Gabancho, M. L., Cabarcos Cazón, A., Duque de las Heras, C., and Miguel de la Villa, F.
- Subjects
Cirrosis alcohólica ,Alcoholic cirrhosis ,Estado nutricional ,Bone disease ,Nutritional state ,Enfermedad ósea - Abstract
Objetivos: Conocer la prevalencia de osteopenia y osteoporosis en cirróticos alcohólicos entre 45 y 65 años de edad. Comprobar si el estado nutricional está implicado en la pérdida de masa ósea de la enfermedad hepática. Material y métodos: Población a estudio: 52 varones cirróticos alcohólicos de 45 a 65 años de edad, con función renal normal, no sedentarios y sin ningún tratamiento que pudiera alterar el estudio. Diseño y variables: estudio descriptivo transversal finalizado en 2 años. El estado nutricional se evaluó por medio de parámetros antropométricos clásicos (peso, altura, perímetro braquial y pliegues cutáneos) y densitometría corporal total (absortimetría de doble haz de RX DPX plus LUNAR-DEXA). Análisis de los datos: ordenador Mc Intosh (programa Filemaker PRO). Se usó la t de Student para comparar grupos y p fue significativo si α
- Published
- 2002
22. Metabolismo óseo y pérdida de masa ósea en los trastornos de la alimentación
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Escalante Boleas, M., Franco Vicario, R., Bustamante Murga, V., and Miguel de la Villa, F.
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Treatments ,Demineralization ,Desmineralización ,Pathophysiology ,Anorexia-bulimia ,Patofisiología ,Tratamientos - Abstract
Los trastornos de la alimentación (anorexia y bulimia nerviosa)afectan al 1-3% de las mujeres jóvenes adultas. Edad tardía de inicio, duración de amenorrea e índice bajo de masa corporal son factores de riesgo de osteopenia en pacientes bulímicas. Se produce desmineralización cuando la reabsorción sobrepasa a la formación ósea en la AN, lo que lleva al desarrollo de osteopenia, osteoporosis secundaria y mayor riesgo de fracturas patológicas. La patofisiología de la desmineralización se atribuye a diversos factores como duración de la amenorrea, deficiente absorción de calcio, ejercicio físico extremo, déficit de 1,25 (OH) vit D, bajo aclaramiento de creatinina, exceso de cortisol sérico y urinario y niveles altos de GH. Los tratamientos recomendados son rehabilitación nutricional (el más importante), suplementos de calcio, ejercicio moderado, terapia estrogénica cuando esté indicada, tratamiento antidepresivo, flúor en casos seleccionados, bifosfonatos e IGF-1 recombinante humano. Un interrogatorio preciso es esencial en mujeres con peso ligeramente descendido y con transtornos menstruales. Eating disorders (anorexia and bulimia nervosa) are present in 1-3% of young female women. A later beginning, prolonged amenorrhea and low body mass index are risk factors of osteopenia in bulimic patients. Bone demineralization in anorexia nervosa is due to a greater resorption than bone formation leading to osteopenia, secondary osteoporosis and increased risk of pathologic fractures. Pathophysiology of bone disease includes factors as long duration of amenorrhea, deficient absorption of calcium, extreme physical exercise, 1,25 vitamin D defficiency, low creatinine clearance, increased blood and urinary cortisol and high levels of GH. Proposed treatments are nutritional improvement and weight gain (the most important), calcium supplementation, moderate exercise, estrogens, antidepressive drugs, fluoride in selected cases, byphosphonates and recombinant human IGF-1. An adequate questionnary is essential in women with slightly decreased weight and mentrual disorders.
- Published
- 2002
23. The Evolution of the Role of Openhole Packers in Advanced Horizontal Completions: From Novel Technology to a Critical Key to Success
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Gavioli, P.., primary and Vicario, R.., additional
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- 2012
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24. OC12.07: Fetal brain development in congenital diaphragmatic hernia.
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Fabietti, I., Savelli, S., Romiti, A., Viggiano, M., Vicario, R., Grassini, G., Nicastri, E., Valfrè, L., Giliberti, P., Capolupo, I., Morini, F., Bagolan, P., and Caforio, L.
- Abstract
It is reported that many infants with CDH have evidence of brain injury on postnatal brain magnetic resonance imaging (MRI). Results HT
ht CF were measured and corrected by biparietal diameter (BPD), obtaining a ratio (CF/BPD) for each fissure measurement to perform the statistical analysis. [Extracted from the article]CDH Controls p Transverse cerebellar diameter (mm) 39 (24-51) 41 (30-49) 0.1533 Anteroposterior vermis length (mm) 13 (9-17) 13 (9-16) 0.3214 Craniocaudal vermis length (mm) 18 (13-25) 19 (13-23) 0.7155 Parietoccipital fissure depth/BPD 0.09 (0.07-0.13) 0.09 (0.05-0.15) 0.6492 Lateral fissure depth/BPD 0.16 (0.13-0.21) 0.16 (0.12-0.19) 0.5901 Cingular fissure depth/BPD 0.06 (0.03-0.10) 0.04 (0.03-0.09) 0.0001 Insular depth/BPD 0.27 (0.24-0.33) 0.28 (0.23-0.33) 0.0149 - Published
- 2022
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25. OC03.04: Management of fetal ovarian cysts based on ultrasound morphology: a new proposal.
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Moro, F., Romiti, A., Ricci, L., Codecà, C., Pozzati, F., Viggiano, M., Vicario, R., Fabietti, I., Biscione, A., Valfrè, L., Scambia, G., Bagolan, P., Testa, A.C., and Caforio, L.
- Abstract
To describe ultrasound features of fetal ovarian cysts as reported by the original ultrasound examiner and according to IOTA terminology. Ovarian cysts with low level content could be managed expectantly, whereas ovarian cysts with other cyst content should be managed with postnatal surgery, due to the high risk of necrosis at final histology. [Extracted from the article]
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- 2022
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26. Nutrición, enfermedad ósea y cirrosis alcohólica
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Escalante Boleas, M. A., primary, Franco Vicario, R., additional, Cubas Largacha, L., additional, Goiría Ormazábal, J. I., additional, Zulueta Gabancho, M. L., additional, Cabarcos Cazón, A., additional, Duque de las Heras, C., additional, and Miguel de la Villa, F., additional
- Published
- 2002
- Full Text
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27. Metabolismo óseo y pérdida de masa ósea en los trastornos de la alimentación
- Author
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Escalante Boleas, M., primary, Franco Vicario, R., additional, Bustamante Murga, V., additional, and Miguel de la Villa, F., additional
- Published
- 2002
- Full Text
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28. Papel de la tipificación genética múltiple (receptores de vitamina D y estrógenos) en la determinación del riesgo de fractura
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Zarrabeitia, M.T., primary, Riancho, J.A., additional, Franco-Vicario, R., additional, Goiria, J., additional, Gonzalo, C., additional, and Gonzêlez-Macías, J., additional
- Published
- 2000
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29. Toward Personal Affordable Exoskeletons With Force Control Capabilities
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Rudy Vicario, Emanuele Palazzi, Eldison Dimo, Davide Costanzi, Andrea Calanca, Rafael Ferro, Rocco Vertechy, Thiago Boaventura, Noè Murr, Matteo Meneghetti, Luca Luzi, Calanca A., Dimo E., Palazzi E., Ferro R., Vicario R., Murr N., Meneghetti M., Costanzi D., Luzi L., Vertechy R., and Boaventura T.
- Subjects
affordability ,Modalities ,Computer science ,Work (physics) ,Control (management) ,Control engineering ,force control ,law.invention ,Exoskeleton ,Controllability ,Microprocessor ,upper-limb exoskeleton ,Interaction control ,law ,Mechanical design - Abstract
This paper presents a design concept for affordable exoskeletons without renouncing to advanced interaction control modalities based on force control technologies. Affordability is reached by (1) lowering the motor requirements, thanks to a smart mechanical design, (2) lowering the sensing requirements, thanks to extensive use of microprocessor DMA, and (3) using low-cost computational platforms. A main finding of this work is that by lowering the motor requirements the exoskeleton improves its inherent force controllability.
- Published
- 2021
30. An Affordable Upper-Limb Exoskeleton Concept for Rehabilitation Applications
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Emanuele Palazzi, Luca Luzi, Eldison Dimo, Matteo Meneghetti, Rudy Vicario, Rafael Ferro Luzia, Rocco Vertechy, Andrea Calanca, Palazzi E., Luzi L., Dimo E., Meneghetti M., Vicario R., Luzia R.F., Vertechy R., and Calanca A.
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affordability ,low cost ,exoskeleton ,mechanical design ,affordable robotics ,rehabilitation robotics ,3D printing ,affordable robotic - Abstract
In recent decades, many researchers have focused on the design and development of exoskeletons. Several strategies have been proposed to develop increasingly more efficient and biomimetic mechanisms. However, existing exoskeletons tend to be expensive and only available for a few people. This paper introduces a new gravity-balanced upper-limb exoskeleton suited for rehabilitation applications and designed with the main objective of reducing the cost of the components and materials. Regarding mechanics, the proposed design significantly reduces the motor torque requirements, because a high cost is usually associated with high-torque actuation. Regarding the electronics, we aim to exploit the microprocessor peripherals to obtain parallel and real-time execution of communication and control tasks without relying on expensive RTOSs. Regarding sensing, we avoid the use of expensive force sensors. Advanced control and rehabilitation features are implemented, and an intuitive user interface is developed. To experimentally validate the functionality of the proposed exoskeleton, a rehabilitation exercise in the form of a pick-and-place task is considered. Experimentally, peak torques are reduced by 89% for the shoulder and by 84% for the elbow.
- Published
- 2022
31. Clonal Hematopoiesis Is Associated With Long-Term Adverse Outcomes Following Cardiac Surgery.
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Ninni S, Vicario R, Coisne A, Woitrain E, Tazibet A, Stewart CM, Diaz LA Jr, White JR, Koussa M, Dubrulle H, Juthier F, Jungling M, Vincentelli A, Edme JL, Nattel S, de Winther M, Geissmann F, Dombrowicz D, Staels B, and Montaigne D
- Subjects
- Aged, Female, Humans, Male, Middle Aged, Dioxygenases genetics, DNA (Cytosine-5-)-Methyltransferases genetics, DNA Methyltransferase 3A, DNA-Binding Proteins genetics, Mutation, Proto-Oncogene Proteins genetics, Repressor Proteins genetics, Risk Assessment methods, Risk Factors, Time Factors, Cardiac Surgical Procedures adverse effects, Clonal Hematopoiesis genetics, Postoperative Complications genetics, Postoperative Complications epidemiology
- Abstract
Background: Cardiac surgery triggers sterile innate immune responses leading to postoperative complications. Clonal hematopoiesis (CH) is associated with short-term inflammation-mediated outcomes after cardiac surgery. The impact of CH on long-term postoperative outcomes remains unknown., Methods and Results: In this cohort study, patients undergoing elective cardiac surgery were included from January 2017 to September 2019. Patients were screened for CH using a predefined gene panel of 19 genes. Recorded clinical events were all-cause death, major adverse cardiac and cerebral events including cardiovascular death, myocardial infarction or nonscheduled coronary revascularization, stroke, and hospitalization for acute heart failure. The primary study outcome was time to a composite criterion including all-cause mortality and major adverse cardiac and cerebral events. Among 314 genotyped patients (median age: 67 years; interquartile range 59-74 years), 139 (44%) presented with CH, based on a variant allelic frequency ≥1%. Carriers of CH had a higher proportion of patients with a history of atrial fibrillation (26% for CH versus 17% for non-CH carriers, P =0.022). The most frequently mutated genes were DNMT3A , TET2 , and ASXL1 . After a median follow-up of 1203 [813-1435] days, the primary outcome occurred in 50 patients. After multivariable adjustment, CH was independently associated with a higher risk for the primary outcome (hazard ratio, 1.88 [95% CI, 1.05-3.41], P =0.035). Most adverse events occurred in patients carrying TET2 variants., Conclusions: In patients undergoing cardiac surgery, CH is frequent and associated with a 2-fold increased long-term risk for major adverse clinical outcomes. CH is a novel risk factor for long-term postcardiac surgery complications and might be useful to personalize management decisions., Registration: URL: https://www.clinicaltrials.gov; Unique identifier: NCT03376165.
- Published
- 2024
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32. A microglia clonal inflammatory disorder in Alzheimer's Disease.
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Vicario R, Fragkogianni S, Weber L, Lazarov T, Hu Y, Hayashi SY, Craddock BP, Socci ND, Alberdi A, Baako A, Ay O, Ogishi M, Lopez-Rodrigo E, Kappagantula R, Viale A, Iacobuzio-Donahue CA, Zhou T, Ransohoff RM, Chesworth R, Abdel-Wahab O, Boisson B, Elemento O, Casanova JL, Miller WT, and Geissmann F
- Abstract
Somatic genetic heterogeneity resulting from post-zygotic DNA mutations is widespread in human tissues and can cause diseases, however few studies have investigated its role in neurodegenerative processes such as Alzheimer's Disease (AD). Here we report the selective enrichment of microglia clones carrying pathogenic variants, that are not present in neuronal, glia/stromal cells, or blood, from patients with AD in comparison to age-matched controls. Notably, microglia-specific AD-associated variants preferentially target the MAPK pathway, including recurrent CBL ring-domain mutations. These variants activate ERK and drive a microglia transcriptional program characterized by a strong neuro-inflammatory response, both in vitro and in patients. Although the natural history of AD-associated microglial clones is difficult to establish in human, microglial expression of a MAPK pathway activating variant was previously shown to cause neurodegeneration in mice, suggesting that AD-associated neuroinflammatory microglial clones may contribute to the neurodegenerative process in patients., Competing Interests: Competing interests. FG has been a paid consultant (no equity) to Third Rock Ventures from 2018 to 2020. Sequencing costs and analysis in this study were covered in part by a SRA between Third Rock venture and MSKCC. This work led to patents PCT/US2022/037893/WO2023004054A1 ‘Methods and compositions for the treatment of alzheimer’s disease’ by MSKCC and PCT/US2018/047964 ‘Kinase mutation-associated neurodegenerative disorders by MSKCC’.
- Published
- 2024
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33. Mechanism of neurodegeneration mediated by clonal inflammatory microglia.
- Author
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Vicario R, Fragkogianni S, Pokrovskii M, Mayer C, Lopez-Rodrigo E, Hu Y, Ogishi M, Alberdi A, Baako A, Ay O, Plu I, Sazdovitch V, Heritier S, Cohen-Aubart F, Shor N, Miyara M, Nguyen-Khac F, Viale A, Idbaih A, Amoura Z, Rosenblum MK, Zhang H, Karnoub ER, Sashittal P, Jakatdar A, Iacobuzio-Donahue CA, Abdel-Wahab O, Tabar V, Socci ND, Elemento O, Diamond EL, Boisson B, Casanova JL, Seilhean D, Haroche J, Donadieu J, and Geissmann F
- Abstract
Langerhans cell Histiocytosis (LCH) and Erdheim-Chester disease (ECD) are clonal myeloid disorders, associated with MAP-Kinase activating mutations and an increased risk of neurodegeneration. Surprisingly, we found pervasive PU.1
+ microglia mutant clones across the brain of LCH and ECD patients with and without neurological symptoms, associated with microgliosis, reactive astrocytosis, and neuronal loss. The disease predominated in the grey nuclei of the rhombencephalon, a topography attributable to a local proliferative advantage of mutant microglia. Presence of clinical symptoms was associated with a longer evolution of the disease and a larger size of PU.1+ clones (p= 0.0003). Genetic lineage tracing of PU.1+ clones suggest a resident macrophage lineage or a bone marrow precursor origin depending on patients. Finally, a CSF1R-inhibitor depleted mutant microglia and limited neuronal loss in mice suggesting an alternative to MAPK inhibitors. These studies characterize a progressive neurodegenerative disease, caused by clonal proliferation of inflammatory microglia (CPIM), with a decade(s)-long preclinical stage of incipient disease that represent a therapeutic window for prevention of neuronal death., Competing Interests: Conflict of Interest. FG has performed consulting for Third Rock venture in the past. Targeted Sequencing was funded in part by a grant from Third Rock venture. FG and RV are inventors in MSKCC’s United States application or PCT international application number PCT/US2018/047964 filed on 8/24/2018 (KINASE MUTATION-ASSOCIATED NEURODEGENERATIVE DISORDERS)- Published
- 2024
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34. Retraction Note: Progesterone receptor assembly of a transcriptional complex along with activator protein 1, signal transducer and activator of transcription 3 and ErbB-2 governs breast cancer growth and predicts response to endocrine therapy.
- Author
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Flaqué MCD, Galigniana NM, Béguelin W, Vicario R, Proietti CJ, Russo RC, Rivas MA, Tkach M, Guzmán P, Roa JC, Maronna E, Pineda V, Muñoz S, Mercogliano MF, Charreau EH, Yankilevich P, Schillaci R, and Elizalde PV
- Published
- 2023
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35. Brain cortical assessment by MRI in fetuses with left congenital diaphragmatic hernia.
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Fabietti I, Grassini G, Savelli S, Vicario R, Romiti A, Viggiano M, Vassallo C, Valfrè L, Giliberti P, Capolupo I, Bonito M, Bagolan P, Morini F, and Caforio L
- Subjects
- Pregnancy, Female, Humans, Ultrasonography, Prenatal methods, Fetus diagnostic imaging, Gestational Age, Brain, Magnetic Resonance Imaging methods, Lung diagnostic imaging, Hernias, Diaphragmatic, Congenital diagnostic imaging
- Abstract
Objective: To evaluate fetal brain development using MRI (magnetic resonance imaging) in CDH (congenital diaphragmatic hernia)., Methods: 52 isolated left CDH and 104 control fetuses were imaged using MRI. Brain morphometry (Biparietal diameter-BPD, brain fronto-occipital diameter-BFOD, third ventricle, posterior ventricles, transcerebellar diameter-TCD, anteroposterior and craniocaudal cerebellar vermis diameter-AP and CC) and cortical structures (bilateral cingulate fissure-CF, insular fissure-IF, insular depth - ID) were compared with controls using Mann-Whitney test., Results: Median gestational age at MRI (p = 0.95)and the median biparietal diameter (p = 0.737) were comparable. Among morphometric parameters, only the brain fronto-occipital diameter was significantly smaller in CDH (p = 0.001) and the third ventricle was significantly greater in CDH (<0.0001). Among cortical structures, the cingulate and insular fissures were significantly deeper in CDH fetuses (p < 0.0001) as the insular depth ID was smaller in CDH (p < 0.03)., Conclusions: CDH fetuses have a smaller fronto-occipital diameter, reduced insular depth, deeper cingulate and insular fissure, and greater third ventricle width as compared to controls. These findings suggest that left CDH may have an impact on fetal brain development with an overall reduction in brain volume., (© 2023 The Authors. Prenatal Diagnosis published by John Wiley & Sons Ltd.)
- Published
- 2023
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36. Hematopoietic Somatic Mosaicism Is Associated With an Increased Risk of Postoperative Atrial Fibrillation.
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Ninni S, Dombrowicz D, Kuznetsova T, Vicario R, Gao V, Molendi-Coste O, Haas J, Woitrain E, Coisne A, Neele AE, Prange K, Willemsen L, Aghezzaf S, Fragkogianni S, Tazibet A, Pineau L, White JR, Eeckhoute J, Koussa M, Dubrulle H, Juthier F, Soquet J, Vincentelli A, Edme JL, de Winther M, Geissmann F, Staels B, and Montaigne D
- Subjects
- Humans, Mosaicism, Aortic Valve surgery, Risk Factors, Postoperative Complications epidemiology, Postoperative Complications genetics, Postoperative Complications diagnosis, Atrial Fibrillation etiology, Atrial Fibrillation genetics, Cardiac Surgical Procedures adverse effects
- Abstract
Background: On-pump cardiac surgery triggers sterile inflammation and postoperative complications such as postoperative atrial fibrillation (POAF). Hematopoietic somatic mosaicism (HSM) is a recently identified risk factor for cardiovascular diseases and results in a shift toward a chronic proinflammatory monocyte transcriptome and phenotype., Objectives: The aim of this study was to assess the prevalence, characteristics, and impact of HSM on preoperative blood and myocardial myeloid cells as well as on outcomes after cardiac surgery., Methods: Blood DNA from 104 patients referred for surgical aortic valve replacement (AVR) was genotyped using the HemePACT panel (576 genes). Four screening methods were applied to assess HSM, and postoperative outcomes were explored. In-depth blood and myocardial leukocyte phenotyping was performed in selected patients using mass cytometry and preoperative and postoperative RNA sequencing analysis of classical monocytes., Results: The prevalence of HSM in the patient cohort ranged from 29%, when considering the conventional HSM panel (97 genes) with variant allelic frequencies ≥2%, to 60% when considering the full HemePACT panel and variant allelic frequencies ≥1%. Three of 4 explored HSM definitions were significantly associated with higher risk for POAF. On the basis of the most inclusive definition, HSM carriers exhibited a 3.5-fold higher risk for POAF (age-adjusted OR: 3.5; 95% CI: 1.52-8.03; P = 0.003) and an exaggerated inflammatory response following AVR. HSM carriers presented higher levels of activated CD64
+ CD14+ CD16- circulating monocytes and inflammatory monocyte-derived macrophages in presurgery myocardium., Conclusions: HSM is frequent in candidates for AVR, is associated with an enrichment of proinflammatory cardiac monocyte-derived macrophages, and predisposes to a higher incidence of POAF. HSM assessment may be useful in the personalized management of patients in the perioperative period. (Post-Operative Myocardial Incident & Atrial Fibrillation [POMI-AF]; NCT03376165)., Competing Interests: Funding Support and Author Disclosures This study was supported by grants from Fédération Française de Cardiologie, Fondation Leducq convention 16CVD01 (“Defining and Targeting Epigenetic Pathways in Monocytes and Macrophages That Contribute to Cardiovascular Disease”), the European Genomic Institute for Diabetes (ANR-10-LABX-0046), Fondation Pour la Recherche Médicale (REFERENCE PROJET EQU202203014650), and Agence Nationale de la Recherche (TOMIS leukocytes: ANR-CE14-0003-01). Dr Staels is a recipient of an Advanced European Research Council Grant (694717). Dr Vicario was supported by the 2018 American Association for Cancer Research–Bristol Myers Squibb Fellowship for Young Investigators in Translational Immuno-Oncology. Work at the Memorial Sloan Kettering Cancer Center (MSKCC) is supported by an MSKCC core grant (P30 CA008748), National Institutes of Health grants 1R01NS115715-01, 1 R01 HL138090-01, and 1 R01 AI130345-01, Basic and Translational Immunology Grants from the Ludwig Center for Cancer Immunotherapy to Dr Geissmann. Dr de Winther is funded by grants from the Netherlands Heart Foundation (CVON: GENIUS2) and the Netherlands Heart Foundation and Spark-Holding (2019B016). Dr Neele is a Dekker fellow of the Netherlands Heart Foundation (2020T029). Dr White is founder and owner of Resphera Biosciences. Dr Geissmann has performed consulting for Third Rock Ventures. Dr Fragkogianni is employed by Tempus Labs. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)- Published
- 2023
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37. Physiological changes in cardiac dimensions and function in low-risk pregnancies.
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Viggiano M, Vassallo C, Massolo AC, Vicario R, Romiti A, Caforio L, and Bagolan P
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- Female, Humans, Pregnancy, Echocardiography
- Published
- 2022
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38. Intrafetal Laser Therapy Is a Feasible Treatment for Different Fetal Conditions: A Systematic Review.
- Author
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Fabietti I, Vassallo C, De Rose DU, Rapisarda A, Romiti A, Viggiano M, Vicario R, Scorletti F, Bonito M, Bagolan P, and Caforio L
- Subjects
- Pregnancy, Infant, Newborn, Humans, Female, Placenta, Pregnancy Outcome, Prenatal Care, Pregnancy, Twin, Premature Birth, Laser Therapy methods
- Abstract
Introduction: Over the past years, intrafetal laser (IFL) therapy has been increasingly used in the management of various prenatal conditions. The aim of our research was to clarify the effectiveness and safety of this technique., Methods: A systematic review of the literature was carried out using MEDLINE/PubMed over a period of 20 years (2001-2021)., Results: A total of forty-one articles were selected in the literature search, including 194 cases of twin reversed arterial perfusion (TRAP) sequence, 56 cases of bronchopulmonary sequestrations (BPSs), 5 cases of placental chorioangiomas (PCA), 11 cases of sacrococcygeal teratoma (SCT), and 103 cases of embryo reduction (ER) managed using IFL. In TRAP sequence, perfusion of the acardiac twin was successfully disrupted in all cases. However, preterm premature rupture of membranes (P-PROMs) occurred in 6 out of 79 pregnancies (7.5%), and preterm birth (PTB) occurred in 36 out of 122 pregnancies (29.5%). In BPS, IFL was successfully performed in all cases with no significant fetal-maternal complications. The rates of P-PROM and PTB were, respectively, 3.2% and 12.5%. All PCA IFL-treated cases resulted in successful pregnancy outcomes; no cases of P-PROM were reported, but the rate of PTB reached a peak of 60% due to complications such as severe fetal growth restriction and fetal Doppler abnormalities. In SCT cases, complete cessation of blood flow was achieved in 4 patients (36.4%); P-PROM occurred in 2 cases (18.2%), whereas the rate of PTB was 87.5%. In ER, no intraoperative or major maternal complications were described in the literature. Rates of miscarriage and PTB differed between initial trichorionic triamniotic and dichorionic triamniotic triplet pregnancies., Conclusion: Our analysis suggests that IFL is a safe and feasible technique for the management of different fetal conditions. However, the overall risk of PTB, and its related morbidity and mortality, ranges from 12.5% in BPS to 87.5% in SCT IFL-treated cases. This information could aid in decision-making during prenatal counseling. However, final perinatal outcome depends on the severity of the disease itself., (© 2022 S. Karger AG, Basel.)
- Published
- 2022
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39. Comparison of mediastinal shift angles obtained with ultrasound and magnetic resonance imaging in fetuses with isolated left sided congenital diaphragmatic hernia.
- Author
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Romiti A, Viggiano M, Savelli S, Salvi S, Vicario R, Vassallo C, Valfrè L, Tomà P, Bonito M, Lanzone A, Bagolan P, and Caforio L
- Subjects
- Female, Fetus diagnostic imaging, Gestational Age, Humans, Lung diagnostic imaging, Magnetic Resonance Imaging, Pregnancy, Retrospective Studies, Ultrasonography, Ultrasonography, Prenatal, Hernias, Diaphragmatic, Congenital diagnostic imaging
- Abstract
Objectives: To compare ultrasound (US) and magnetic resonance imaging (MRI) in the assessment of mediastinal shift angles (MSAs) in fetuses affected by isolated left congenital diaphragmatic hernia (CDH). The use of MRI-MSA and US-MSA as prognostic factor for postnatal survival in fetal left CDH was also explored., Methods: This was an observational study of 29 fetuses with prenatally diagnosed isolated left CDH, assessed with both US and MRI examinations between January 2015 and December 2018. The US-MSA measurements performed within 2 weeks from the MRI assessment were considered for the analysis. The primary outcome was the postnatal survival rate., Results: No significant difference between US and MRI MSAs was detected ( p = .419). Among the 29 cases, there were 21 alive infants, for an overall postnatal survival rate of 72.41%. After stratifying for postnatal survival, the best cutoffs with the highest discriminatory power in terms of sensibility and specificity were 42.1° for the US-MSA and 39.1° for the MRI-MSA. The performance of MRI-MSA in predicting postnatal survival was close to that of US-MSA in terms of sensitivity (62.5 versus 50.0%), specificity (80.9 versus 90.5%), positive predictive value (55.6 versus 66.7%), negative predictive value (85.0 versus 82.6%) and accuracy (75.9 versus 79.3%). There was no statistically significant difference between the two modalities ( p > .05 for all)., Conclusions: MRI and US can be interchangeably used for the assessment of MSA in prenatally diagnosed isolated left CDH. Moreover, MSA measured by both US and MRI was confirmed to be correlated with perinatal outcome in terms of survival.
- Published
- 2022
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40. Toward autonomous robotic prostate biopsy: a pilot study.
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Maris B, Tenga C, Vicario R, Palladino L, Murr N, De Piccoli M, Calanca A, Puliatti S, Micali S, Tafuri A, and Fiorini P
- Subjects
- Biopsy, Needle methods, Humans, Magnetic Resonance Imaging methods, Male, Phantoms, Imaging, Pilot Projects, Ultrasonography, Image Processing, Computer-Assisted methods, Image-Guided Biopsy methods, Prostatic Neoplasms diagnosis, Robotics methods, Software
- Abstract
Purpose: We present the validation of PROST, a robotic device for prostate biopsy. PROST is designed to minimize human error by introducing some autonomy in the execution of the key steps of the procedure, i.e., target selection, image fusion and needle positioning. The robot allows executing a targeted biopsy through ultrasound (US) guidance and fusion with magnetic resonance (MR) images, where the target was defined., Methods: PROST is a parallel robot with 4 degrees of freedom (DOF) to orient the needle and 1 DOF to rotate the US probe. We reached a calibration error of less than 2 mm, computed as the difference between the needle positioning in robot coordinates and in the US image. The autonomy of the robot is given by the image analysis software, which employs deep learning techniques, the integrated image fusion algorithms and automatic computation of the needle trajectory. For safety reasons, the insertion of the needle is assigned to the doctor., Results: System performance was evaluated in terms of positioning accuracy. Tests were performed on a 3D printed object with nine 2-mm spherical targets and on an anatomical commercial phantom that simulates human prostate with three lesions and the surrounding structures. The average accuracy reached in the laboratory experiments was [Formula: see text] in the first test and [Formula: see text] in the second test., Conclusions: We introduced a first prototype of a prostate biopsy robot that has the potential to increase the detection of clinically significant prostate cancer and, by including some level of autonomy, to simplify the procedure, to reduce human errors and shorten training time. The use of a robot for the biopsy of the prostate will create the possibility to include also a treatment, such as focal ablation, to be delivered through the same system., (© 2021. The Author(s).)
- Published
- 2021
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41. Origins, Biology, and Diseases of Tissue Macrophages.
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Cox N, Pokrovskii M, Vicario R, and Geissmann F
- Subjects
- Animals, Biology, Humans, Hematopoietic Stem Cells, Macrophages
- Abstract
Tissue-resident macrophages are present in most tissues with developmental, self-renewal, or functional attributes that do not easily fit into a textbook picture of a plastic and multifunctional macrophage originating from hematopoietic stem cells; nor does it fit a pro- versus anti-inflammatory paradigm. This review presents and discusses current knowledge on the developmental biology of macrophages from an evolutionary perspective focused on the function of macrophages, which may aid in study of developmental, inflammatory, tumoral, and degenerative diseases. We also propose a framework to investigate the functions of macrophages in vivo and discuss how inherited germline and somatic mutations may contribute to the roles of macrophages in diseases.
- Published
- 2021
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42. Actuation Selection for Assistive Exoskeletons: Matching Capabilities to Task Requirements.
- Author
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Calanca A, Toxiri S, Costanzi D, Sartori E, Vicario R, Poliero T, Natali CD, Caldwell DG, Fiorini P, and Ortiz J
- Subjects
- Equipment Design, Humans, Orthotic Devices, Torque, Exoskeleton Device
- Abstract
Selecting actuators for assistive exoskeletons involves decisions in which designers usually face contrasting requirements. While certain choices may depend on the application context or design philosophy, it is generally desirable to avoid oversizing actuators in order to obtain more lightweight and transparent systems, ultimately promoting the adoption of a given device. In many cases, the torque and power requirements can be relaxed by exploiting the contribution of an elastic element acting in mechanical parallel. This contribution considers one such case and introduces a methodology for the evaluation of different actuator choices resulting from the combination of different motors, reduction gears, and parallel stiffness profiles, helping to match actuator capabilities to the task requirements. Such methodology is based on a graphical tool showing how different design choices affect the actuator as a whole. To illustrate the approach, a back-support exoskeleton for lifting tasks is considered as a case study.
- Published
- 2020
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43. p95HER2-T cell bispecific antibody for breast cancer treatment.
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Rius Ruiz I, Vicario R, Morancho B, Morales CB, Arenas EJ, Herter S, Freimoser-Grundschober A, Somandin J, Sam J, Ast O, Barriocanal ÁM, Luque A, Escorihuela M, Varela I, Cuartas I, Nuciforo P, Fasani R, Peg V, Rubio I, Cortés J, Serra V, Escriva-de-Romani S, Sperinde J, Chenna A, Huang W, Winslow J, Albanell J, Seoane J, Scaltriti M, Baselga J, Tabernero J, Umana P, Bacac M, Saura C, Klein C, and Arribas J
- Subjects
- Animals, Breast Neoplasms pathology, CD3 Complex immunology, Cell Line, Tumor, Cell Proliferation, Female, Humans, Mice, Xenograft Model Antitumor Assays, Antibodies, Bispecific therapeutic use, Breast Neoplasms drug therapy, Breast Neoplasms immunology, Receptor, ErbB-2 immunology, T-Lymphocytes immunology
- Abstract
T cell bispecific antibodies (TCBs) are engineered molecules that include, within a single entity, binding sites to the T cell receptor and to tumor-associated or tumor-specific antigens. The receptor tyrosine kinase HER2 is a tumor-associated antigen in ~25% of breast cancers. TCBs targeting HER2 may result in severe toxicities, likely due to the expression of HER2 in normal epithelia. About 40% of HER2-positive tumors express p95HER2, a carboxyl-terminal fragment of HER2. Using specific antibodies, here, we show that p95HER2 is not expressed in normal tissues. We describe the development of p95HER2-TCB and show that it has a potent antitumor effect on p95HER2-expressing breast primary cancers and brain lesions. In contrast with a TCB targeting HER2, p95HER2-TCB has no effect on nontransformed cells that do not overexpress HER2. These data pave the way for the safe treatment of a subgroup of HER2-positive tumors by targeting a tumor-specific antigen., (Copyright © 2018 The Authors, some rights reserved; exclusive licensee American Association for the Advancement of Science. No claim to original U.S. Government Works.)
- Published
- 2018
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44. Gasdermin B expression predicts poor clinical outcome in HER2-positive breast cancer.
- Author
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Hergueta-Redondo M, Sarrio D, Molina-Crespo Á, Vicario R, Bernadó-Morales C, Martínez L, Rojo-Sebastián A, Serra-Musach J, Mota A, Martínez-Ramírez Á, Castilla MÁ, González-Martin A, Pernas S, Cano A, Cortes J, Nuciforo PG, Peg V, Palacios J, Pujana MÁ, Arribas J, and Moreno-Bueno G
- Subjects
- Adult, Aged, Animals, Antineoplastic Agents, Immunological pharmacology, Antineoplastic Agents, Immunological therapeutic use, Biomarkers, Tumor genetics, Biomarkers, Tumor metabolism, Breast Neoplasms mortality, Breast Neoplasms pathology, Breast Neoplasms therapy, Carcinoma, Ductal, Breast mortality, Carcinoma, Ductal, Breast pathology, Carcinoma, Ductal, Breast therapy, Chemotherapy, Adjuvant, Disease-Free Survival, Drug Resistance, Neoplasm, Female, Follow-Up Studies, Gene Amplification, Humans, Lymphatic Metastasis, Mice, Mice, Nude, Middle Aged, Neoadjuvant Therapy, Neoplasm Proteins metabolism, Neoplasm Recurrence, Local mortality, Neoplasm Recurrence, Local pathology, Neoplasm Recurrence, Local therapy, Prognosis, Receptor, ErbB-2 metabolism, Trastuzumab pharmacology, Trastuzumab therapeutic use, Xenograft Model Antitumor Assays, Breast Neoplasms genetics, Carcinoma, Ductal, Breast genetics, Gene Expression Regulation, Neoplastic, Neoplasm Proteins genetics, Neoplasm Recurrence, Local genetics, Receptor, ErbB-2 antagonists & inhibitors
- Abstract
Around, 30-40% of HER2-positive breast cancers do not show substantial clinical benefit from the targeted therapy and, thus, the mechanisms underlying resistance remain partially unknown. Interestingly, ERBB2 is frequently co-amplified and co-expressed with neighbour genes that may play a relevant role in this cancer subtype. Here, using an in silico analysis of data from 2,096 breast tumours, we reveal a significant correlation between Gasdermin B (GSDMB) gene (located 175 kilo bases distal from ERBB2) expression and the pathological and clinical parameters of poor prognosis in HER2-positive breast cancer. Next, the analysis of three independent cohorts (totalizing 286 tumours) showed that approximately 65% of the HER2-positive cases have GSDMB gene amplification and protein over-expression. Moreover, GSDMB expression was also linked to poor therapeutic responses in terms of lower relapse free survival and pathologic complete response as well as positive lymph node status and the development of distant metastasis under neoadjuvant and adjuvant treatment settings, respectively. Importantly, GSDMB expression promotes survival to trastuzumab in different HER2-positive breast carcinoma cells, and is associated with trastuzumab resistance phenotype in vivo in Patient Derived Xenografts. In summary, our data identifies the ERBB2 co-amplified and co-expressed gene GSDMB as a critical determinant of poor prognosis and therapeutic response in HER2-positive breast cancer., Competing Interests: The authors declare that they have no conflicts of interests.
- Published
- 2016
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45. High HER2 protein levels correlate with increased survival in breast cancer patients treated with anti-HER2 therapy.
- Author
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Nuciforo P, Thyparambil S, Aura C, Garrido-Castro A, Vilaro M, Peg V, Jimenez J, Vicario R, Cecchi F, Hoos W, Burrows J, Hembrough T, Ferreres JC, Perez-Garcia J, Arribas J, Cortes J, and Scaltriti M
- Subjects
- Antibodies, Monoclonal, Humanized therapeutic use, Breast Neoplasms metabolism, Female, Humans, Lapatinib, Mass Spectrometry, Quinazolines therapeutic use, Receptor, ErbB-2 antagonists & inhibitors, Survival Analysis, Trastuzumab therapeutic use, Breast Neoplasms drug therapy, Receptor, ErbB-2 metabolism
- Abstract
Introduction: Current methods to determine HER2 (human epidermal growth factor receptor 2) status are affected by reproducibility issues and do not reliably predict benefit from anti-HER2 therapy. Quantitative measurement of HER2 may more accurately identify breast cancer (BC) patients who will respond to anti-HER2 treatments., Methods: Using selected reaction monitoring mass spectrometry (SRM-MS), we quantified HER2 protein levels in formalin-fixed, paraffin-embedded (FFPE) tissue samples that had been classified as HER2 0, 1+, 2+ or 3+ by immunohistochemistry (IHC). Receiver operator curve (ROC) analysis was conducted to obtain optimal HER2 protein expression thresholds predictive of HER2 status (by standard IHC or in situ hybridization [ISH]) and of survival benefit after anti-HER2 therapy., Results: Absolute HER2 amol/μg levels were significantly correlated with both HER2 IHC and amplification status by ISH (p < 0.0001). A HER2 threshold of 740 amol/μg showed an agreement rate of 94% with IHC and ISH standard HER2 testing (p < 0.0001). Discordant cases (SRM-MS-negative/ISH-positive) showed a characteristic amplification pattern known as double minutes. HER2 levels >2200 amol/μg were significantly associated with longer disease-free survival (DFS) and overall survival (OS) in an adjuvant setting and with longer OS in a metastatic setting., Conclusion: Quantitative HER2 measurement by SRM-MS is superior to IHC and ISH in predicting outcome after treatment with anti-HER2 therapy., (Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.)
- Published
- 2016
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46. Patterns of HER2 Gene Amplification and Response to Anti-HER2 Therapies.
- Author
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Vicario R, Peg V, Morancho B, Zacarias-Fluck M, Zhang J, Martínez-Barriocanal Á, Navarro Jiménez A, Aura C, Burgues O, Lluch A, Cortés J, Nuciforo P, Rubio IT, Marangoni E, Deeds J, Boehm M, Schlegel R, Tabernero J, Mosher R, and Arribas J
- Subjects
- Animals, Antineoplastic Agents pharmacology, Cell Line, Tumor, Disease Models, Animal, Drug Resistance, Neoplasm, Female, Gene Dosage, Humans, Lapatinib, Quinazolines pharmacology, Quinazolines therapeutic use, Trastuzumab pharmacology, Trastuzumab therapeutic use, Treatment Outcome, Xenograft Model Antitumor Assays, Antineoplastic Agents therapeutic use, Breast Neoplasms drug therapy, Breast Neoplasms genetics, Gene Amplification, Molecular Targeted Therapy, Receptor, ErbB-2 antagonists & inhibitors, Receptor, ErbB-2 genetics
- Abstract
A chromosomal region that includes the gene encoding HER2, a receptor tyrosine kinase (RTK), is amplified in 20% of breast cancers. Although these tumors tend to respond to drugs directed against HER2, they frequently become resistant and resume their malignant progression. Gene amplification in double minutes (DMs), which are extrachromosomal entities whose number can be dynamically regulated, has been suggested to facilitate the acquisition of resistance to therapies targeting RTKs. Here we show that ~30% of HER2-positive tumors show amplification in DMs. However, these tumors respond to trastuzumab in a similar fashion than those with amplification of the HER2 gene within chromosomes. Furthermore, in different models of resistance to anti-HER2 therapies, the number of DMs containing HER2 is maintained, even when the acquisition of resistance is concomitant with loss of HER2 protein expression. Thus, both clinical and preclinical data show that, despite expectations, loss of HER2 protein expression due to loss of DMs containing HER2 is not a likely mechanism of resistance to anti-HER2 therapies.
- Published
- 2015
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47. Effect of cellular senescence on the growth of HER2-positive breast cancers.
- Author
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Zacarias-Fluck MF, Morancho B, Vicario R, Luque Garcia A, Escorihuela M, Villanueva J, Rubio IT, and Arribas J
- Subjects
- Animals, Cell Line, Tumor, Cell Proliferation, Female, Gene Expression Regulation, Neoplastic, Heterografts, Humans, Interleukin-6 metabolism, Mice, Mice, Transgenic, Microscopy, Confocal, Up-Regulation, Biomarkers, Tumor analysis, Breast Neoplasms chemistry, Breast Neoplasms pathology, Cellular Senescence, Receptor, ErbB-2 analysis
- Abstract
Background: Oncogene-induced senescence (OIS) is a tumor suppressor mechanism. However, senescent cells remain viable and display a distinct secretome (also known as senescence-associated secretory phenotype [SASP] or senescence messaging secretome, [SMS]) that, paradoxically, includes protumorigenic factors. OIS can be triggered by ectopic overexpression of HER2, a receptor tyrosine kinase and the driving oncogene in a subtype of human breast cancer. However, cellular senescence has not been characterized in HER2-positive tumors., Methods: Using an approach based on their inability to proliferate, we isolated naturally occurring senescent cells from a variety of tumor models including HER2-positive cells, transgenic mice (n = 3), and patient-derived xenografts (PDXs) (n = 6 mice per group from one PDX derived from one patient). Using different biochemical and cell biological techniques, we characterized the secretome of these senescent cells. All statistical tests were two-sided., Results: We found that senescent cells arise constantly in different models of advanced breast cancers overexpressing HER2 and constitute approximately 5% of tumor cells. In these models, IL-6 and other cytokines were expressed mainly, if not exclusively, by the naturally occurring senescent cells (95.1% and 45.0% of HCC1954 cells and cells from a HER2-positive PDX expressing a senescent marker expressed IL-6, respectively). Furthermore, inhibition of IL-6 impaired the growth of the HER2-positive PDX (mean tumor volume at day 101, control vs anti-huIL-6 treated, 332.2mm(3) [95% confidence interval {CI} = 216.6 to 449.8] vs 114.4mm(3) [95% CI = 12.79 to 216.0], P = .005)., Conclusions: Senescent cells can contribute to the growth of tumors by providing cytokines not expressed by proliferating cells, but required by these to thrive., (© The Author 2015. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2015
- Full Text
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48. Transabdominal coelocentesis as early source of fetal DNA for chromosomal and molecular diagnosis.
- Author
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Pietropolli A, Vicario R, Peconi C, Zampatti S, Quitadamo MC, Capogna MV, Ragazzo M, Nardone AM, Postorivo D, Spitalieri P, Sarta S, Ratto F, Novelli G, Sangiuolo F, Piccione E, and Giardina E
- Subjects
- Adult, Comparative Genomic Hybridization, Female, Genetic Testing, Humans, Polymerase Chain Reaction, Pregnancy, Prospective Studies, Young Adult, Paracentesis methods, Prenatal Diagnosis methods
- Abstract
This study reports a comparative analysis between results of transabdominal coelocentesis and traditional invasive procedure in order to assess the usefulness of coelocentesis as a source of fetal DNA for molecular and chromosomal analysis. A number of 28 women were included in the study. A successful sampling of coelomic fluid was obtained in 25 women by transabdominal procedure. A positive amplification of DNA with QF-PCR techniques was obtained in 90% of cases, while 10% of cases failed to reveal interpretable results. Although all samples were cultured, the growth rate was not sufficient to determine karyotypes within 2 weeks. Five samples were selected to be analyzed by array-based comparative genomic hybridization (a-CGH) but the interpretation of these results was difficult and ambiguous. Our results suggest that transabdominal coelocentesis is suitable for the detection of single DNA variation and for QF-PCR analysis, while further experiments are needed to develop optimized protocols for traditional karyotyping and array-analysis.
- Published
- 2014
- Full Text
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49. Effect of p95HER2/611CTF on the response to trastuzumab and chemotherapy.
- Author
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Parra-Palau JL, Morancho B, Peg V, Escorihuela M, Scaltriti M, Vicario R, Zacarias-Fluck M, Pedersen K, Pandiella A, Nuciforo P, Serra V, Cortés J, Baselga J, Perou CM, Prat A, Rubio IT, and Arribas J
- Subjects
- Animals, Anthracyclines administration & dosage, Cell Proliferation, Doxorubicin administration & dosage, Female, Flow Cytometry, Gene Expression Profiling, Humans, Immunohistochemistry, Mice, Microscopy, Confocal, Receptor, ErbB-2 drug effects, Taxoids administration & dosage, Trastuzumab, Xenograft Model Antitumor Assays, Antibodies, Monoclonal, Humanized pharmacology, Antineoplastic Agents pharmacology, Antineoplastic Combined Chemotherapy Protocols therapeutic use, Breast Neoplasms drug therapy, Breast Neoplasms metabolism, Receptor, ErbB-2 metabolism
- Abstract
Human epidermal growth factor receptor 2 (HER2)-positive breast cancers are currently treated with trastuzumab, an anti-HER2 antibody. About 30% of these tumors express a group of HER2 fragments collectively known as p95HER2. Our previous work indicated that p95HER2-positive tumors are resistant to trastuzumab monotherapy. However, recent results showed that tumors expressing the most active of these fragments, p95HER2/611CTF, respond to trastuzumab plus chemotherapy. To clarify this discrepancy, we analyzed the response to chemotherapy of cell lines transfected with p95HER2/611CTF and patient-derived xenografts (n = 7 mice per group) with different levels of the fragment. All statistical tests were two-sided. p95HER2/611CTF-negative and positive tumors showed different responses to various chemotherapeutic agents, which are particularly effective on p95HER2/611CTF-positive cells. Furthermore, chemotherapy sensitizes p95HER2/611CTF-positive patient-derived xenograft tumors to trastuzumab (mean tumor volume, trastuzumab alone: 906 mm(3), 95% confidence interval = 1274 to 538 mm(3); trastuzumab+doxorubicin: 259 mm(3), 95% confidence interval = 387 to 131 mm(3); P < .001). This sensitization may be related to HER2 stabilization induced by chemotherapy in p95HER2/611CTF-positive cells., (© The Author 2014. Published by Oxford University Press. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)
- Published
- 2014
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50. Progesterone receptor assembly of a transcriptional complex along with activator protein 1, signal transducer and activator of transcription 3 and ErbB-2 governs breast cancer growth and predicts response to endocrine therapy.
- Author
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Díaz Flaqué MC, Galigniana NM, Béguelin W, Vicario R, Proietti CJ, Russo R, Rivas MA, Tkach M, Guzmán P, Roa JC, Maronna E, Pineda V, Muñoz S, Mercogliano M, Charreau EH, Yankilevich P, Schillaci R, and Elizalde PV
- Subjects
- Animals, Breast Neoplasms mortality, Breast Neoplasms pathology, Cell Nucleus drug effects, Cyclin D1 genetics, Cyclin D1 metabolism, Female, Follow-Up Studies, Humans, Medroxyprogesterone Acetate pharmacology, Mice, Inbred BALB C, Phosphorylation drug effects, Promoter Regions, Genetic, Receptor, ErbB-2 genetics, Retrospective Studies, Selective Estrogen Receptor Modulators therapeutic use, Tamoxifen therapeutic use, Treatment Outcome, Breast Neoplasms drug therapy, Breast Neoplasms metabolism, Receptor, ErbB-2 metabolism, Receptors, Progesterone metabolism, STAT3 Transcription Factor metabolism, Transcription Factor AP-1 metabolism
- Abstract
Introduction: The role of the progesterone receptor (PR) in breast cancer remains a major clinical challenge. Although PR induces mammary tumor growth, its presence in breast tumors is a marker of good prognosis. We investigated coordinated PR rapid and nonclassical transcriptional effects governing breast cancer growth and endocrine therapy resistance., Methods: We used breast cancer cell lines expressing wild-type and mutant PRs, cells sensitive and resistant to endocrine therapy, a variety of molecular and cellular biology approaches, in vitro proliferation studies and preclinical models to explore PR regulation of cyclin D1 expression, tumor growth, and response to endocrine therapy. We investigated the clinical significance of activator protein 1 (AP-1) and PR interaction in a cohort of 99 PR-positive breast tumors by an immunofluorescence protocol we developed. The prognostic value of AP-1/PR nuclear colocalization in overall survival (OS) was evaluated using Kaplan-Meier method, and Cox model was used to explore said colocalization as an independent prognostic factor for OS., Results: We demonstrated that at the cyclin D1 promoter and through coordinated rapid and transcriptional effects, progestin induces the assembly of a transcriptional complex among AP-1, Stat3, PR, and ErbB-2 which functions as an enhanceosome to drive breast cancer growth. Our studies in a cohort of human breast tumors identified PR and AP-1 nuclear interaction as a marker of good prognosis and better OS in patients treated with tamoxifen (Tam), an anti-estrogen receptor therapy. Rationale for this finding was provided by our demonstration that Tam inhibits rapid and genomic PR effects, rendering breast cancer cells sensitive to its antiproliferative effects., Conclusions: We here provided novel insight into the paradox of PR action as well as new tools to identify the subgroup of ER+/PR + patients unlikely to respond to ER-targeted therapies.
- Published
- 2013
- Full Text
- View/download PDF
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