41 results on '"Vicario R"'
Search Results
2. Dimensional and form errors of PC parts printed via Fused Deposition Modelling
- Author
-
Reyes-Rodríguez, A., Dorado-Vicente, R., and Mayor-Vicario, R.
- Published
- 2017
- Full Text
- View/download PDF
3. Using IOTA terminology to evaluate fetal ovarian cysts: analysis of 51 cysts over 10‐year period.
- Author
-
Romiti, A., Moro, F., Ricci, L., Codeca, C., Pozzati, F., Viggiano, M., Vicario, R., Fabietti, I., Scambia, G., Bagolan, P., Testa, A. C., and Caforio, L.
- Subjects
OVARIAN cysts ,FETAL ultrasonic imaging ,PRENATAL diagnosis ,IMAGE analysis ,CYSTS (Pathology) ,CHILDREN'S hospitals ,ULTRASONIC imaging - Abstract
Objectives: To describe ultrasound features of fetal ovarian cysts as reported by the original ultrasound examiner, to apply International Ovarian Tumor Analysis (IOTA) terminology after retrospective analysis of the images and to describe patient management and evolution of fetal cysts during pregnancy and after delivery. Methods: This retrospective observational study included pregnant women diagnosed on ultrasound examination with a fetal ovarian cyst at the Prenatal Diagnosis Division of the Bambino Gesù Children's Hospital, in Rome, between March 2011 and May 2020. Cysts were classified by the original ultrasound examiner as 'simple' (unilocular anechoic cyst) or 'complex' (cyst with other morphology). In addition, three ultrasound examiners, experienced in gynecologic ultrasound, classified retrospectively the fetal ovarian cysts according to IOTA terminology, by reviewing stored ultrasound images. The evolution of these fetal ovarian cysts during pregnancy and after birth was recorded. Results: Included were 51 ovarian cysts in 48 fetuses. Of the 51 cysts, 29 (56.9%) had been classified by the original ultrasound examiner as 'simple', and 22 (43.1%) as 'complex'. Of the simple cysts, the majority (20/29 (69.0%)) resolved spontaneously after delivery, 2/29 (6.9%) resolved following intrauterine aspiration, 2/29 (6.9%) resolved after postnatal aspiration and 5/29 (17.2%) underwent surgery due to persistence after delivery; in all five, normal ovarian parenchyma without signs of necrosis was observed at histology. Of the complex cysts, 7/22 (31.8%) resolved spontaneously. The other 15/22 (68.2%) were removed surgically and, at histology, necrosis was observed in most (12/15 (80.0%)), while a benign epithelial cyst with normal ovarian parenchyma was observed in 3/15 (20%). After reviewing the ultrasound images and applying IOTA terminology, all 51 (100%) fetal cysts were described as unilocular; 29/51 (56.9%) cysts showed anechoic content (described as simple cysts by the original ultrasound examiner), and 10/51 (19.6%) had low‐level, 1/51 (2.0%) had ground‐glass, 9/51 (17.6%) had hemorrhagic, 1/51 (2.0%) had mixed and 1/51 (2.0%) had undefined content (all described as complex by the original ultrasound examiner). Among the 29 anechoic ovarian cysts, resolution was observed in most (24/29, 82.8%) cases. Similarly, resolution was observed in 7/10 (70.0%) cysts with low‐level content. Resolution was not observed in any of the other 12 cysts and all of these cases underwent surgery, with evidence of necrosis being observed in 11 (91.7%). Conclusions: Applying IOTA terminology provided a more detailed and accurate description of fetal ovarian cysts compared with the original classification into 'simple' and 'complex' categories. Anechoic cysts (described as simple cysts by the original ultrasound examiner) and cysts with low‐level content (described as complex by the original ultrasound examiner) frequently resolved spontaneously. Cysts with ground‐glass, hemorrhagic, mixed or undefined content were frequently associated with necrosis at histology following surgery. © 2022 The Authors. Ultrasound in Obstetrics & Gynecology published by John Wiley & Sons Ltd on behalf of International Society of Ultrasound in Obstetrics and Gynecology. [ABSTRACT FROM AUTHOR]
- Published
- 2023
- Full Text
- View/download PDF
4. Hypersensitivity pneumonitis induced by exposure to the legume algarroba
- Author
-
Franco-Vicario, R., Gamboa, P., Escalante, M., Pueyo, V., Sanz, M. L., Solano, D., and Miguel, F.
- Published
- 1997
5. SC218 - Transperineal robotic prostate biopsy with prost: a pilot study
- Author
-
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
- Full Text
- View/download PDF
6. SC344 - The asymptomatic, high-grade refluxing male. ciinical follow up of a new cohort of patients derived from prenatal diagnosis
- Author
-
Zaccara, A., Lais, A., Capitanucci, M.L., Mosiello, G., Silveri, M., Vicario, R., Romiti, A., Viggiano, M., and Caforio, L.
- Published
- 2020
- Full Text
- View/download PDF
7. New Software for Valutation of Uterine Septum
- Author
-
Marziali, M, Pedone, M, and Vicario, R
- Published
- 2016
- Full Text
- View/download PDF
8. Hysteroscopic Polypectomy on the Day of Egg Retrieval, 5 Days Prior to Embryo Transfer: A Case Report
- Author
-
García-Guzmán, R, Rouleau, JP, Hernández, J, Vicario, R, Pirollo, L, and Palumbo, A
- Published
- 2016
- Full Text
- View/download PDF
9. Accuracy of Three-Dimensional Saline Infusion Sonohysterography (3D-SIS) for Evaluation of Uterine Cavity Abnormalities in Infertility Patients
- Author
-
Rouleau, JP, Rodriguez Fuentes, A, Pirollo, L, Vicario, R, Costa, M, Hernandez, J, Garcia Guzman, R, and Palumbo, A
- Published
- 2016
- Full Text
- View/download PDF
10. OC12.07: Fetal brain development in congenital diaphragmatic hernia.
- Author
-
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
- Full Text
- View/download PDF
11. OC03.04: Management of fetal ovarian cysts based on ultrasound morphology: a new proposal.
- Author
-
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]
- Published
- 2022
- Full Text
- View/download PDF
12. The Evolution of the Role of Openhole Packers in Advanced Horizontal Completions: From Novel Technology to a Critical Key to Success.
- Author
-
Gavioli, R. and Vicario, R.
- Subjects
WELL packers ,GAS flow ,HYDRAULICS ,OIL well drilling ,OIL field equipment - Abstract
The article discusses the significant role played by openhole isolation technology on the success of advanced horizontal completions. It says that the most important function of openhole packers is their ability to control the flow of gas or water after breakthrough. Meanwhile, it presents the factors to be considered when choosing the appropriate packer for a certain oil well drilling application.
- Published
- 2012
- Full Text
- View/download PDF
13. VP15.07: Physiological changes in cardiac dimensions and function in low‐risk pregnancies.
- Author
-
Viggiano, M., Vassallo, C., Massolo, A., Vicario, R., Romiti, A., Bagolan, P., and Caforio, L.
- Subjects
PREGNANCY ,FETAL diseases ,TRICUSPID valve ,MITRAL valve - Published
- 2020
- Full Text
- View/download PDF
14. 303: A role for senescent cell-derived IL6 in HER2+ breast cancer progression.
- Author
-
Zacarias Fluck, M., Morancho, B., Angelini, P.D., Vicario, R., Villarreal, L., Aura, C., Nuciforo, P., Villanueva, J., Rubio, I.T., and Arribas, J.
- Published
- 2014
- Full Text
- View/download PDF
15. 306: Chemotherapy sensitizes p95HER2-positive breast cancers to trastuzumab.
- Author
-
Morancho, B., Parra-Palau, J.L., Peg, V., Vicario, R., Zacarias-Fluck, M., Pedersen, K., Perou, C.M., Prat, A., Rubio, I.T., and Arribas, J.
- Published
- 2014
- Full Text
- View/download PDF
16. Clonal Hematopoiesis Is Associated With Long-Term Adverse Outcomes Following Cardiac Surgery.
- Author
-
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
- Full Text
- View/download PDF
17. A microglia clonal inflammatory disorder in Alzheimer's Disease.
- Author
-
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
- Full Text
- View/download PDF
18. Mechanism of neurodegeneration mediated by clonal inflammatory microglia.
- Author
-
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
- Full Text
- View/download PDF
19. 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
-
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
- Full Text
- View/download PDF
20. Brain cortical assessment by MRI in fetuses with left congenital diaphragmatic hernia.
- Author
-
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
- Full Text
- View/download PDF
21. Hematopoietic Somatic Mosaicism Is Associated With an Increased Risk of Postoperative Atrial Fibrillation.
- Author
-
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
- Full Text
- View/download PDF
22. Physiological changes in cardiac dimensions and function in low-risk pregnancies.
- Author
-
Viggiano M, Vassallo C, Massolo AC, Vicario R, Romiti A, Caforio L, and Bagolan P
- Subjects
- Female, Humans, Pregnancy, Echocardiography
- Published
- 2022
- Full Text
- View/download PDF
23. Comparison of mediastinal shift angles obtained with ultrasound and magnetic resonance imaging in fetuses with isolated left sided congenital diaphragmatic hernia.
- Author
-
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
- Full Text
- View/download PDF
24. Intrafetal Laser Therapy Is a Feasible Treatment for Different Fetal Conditions: A Systematic Review.
- Author
-
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
- Full Text
- View/download PDF
25. Toward autonomous robotic prostate biopsy: a pilot study.
- Author
-
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
- Full Text
- View/download PDF
26. Origins, Biology, and Diseases of Tissue Macrophages.
- Author
-
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
- Full Text
- View/download PDF
27. Actuation Selection for Assistive Exoskeletons: Matching Capabilities to Task Requirements.
- Author
-
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
- Full Text
- View/download PDF
28. p95HER2-T cell bispecific antibody for breast cancer treatment.
- Author
-
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
- Full Text
- View/download PDF
29. Gasdermin B expression predicts poor clinical outcome in HER2-positive breast cancer.
- Author
-
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
- Full Text
- View/download PDF
30. High HER2 protein levels correlate with increased survival in breast cancer patients treated with anti-HER2 therapy.
- Author
-
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
- Full Text
- View/download PDF
31. Patterns of HER2 Gene Amplification and Response to Anti-HER2 Therapies.
- Author
-
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
- Full Text
- View/download PDF
32. Effect of cellular senescence on the growth of HER2-positive breast cancers.
- Author
-
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
- View/download PDF
33. Transabdominal coelocentesis as early source of fetal DNA for chromosomal and molecular diagnosis.
- Author
-
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
- View/download PDF
34. Effect of p95HER2/611CTF on the response to trastuzumab and chemotherapy.
- Author
-
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
- Full Text
- View/download PDF
35. 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
-
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
36. Progestin drives breast cancer growth by inducing p21(CIP1) expression through the assembly of a transcriptional complex among Stat3, progesterone receptor and ErbB-2.
- Author
-
Diaz Flaqué MC, Vicario R, Proietti CJ, Izzo F, Schillaci R, and Elizalde PV
- Subjects
- Animals, Breast Neoplasms genetics, Cyclin-Dependent Kinase Inhibitor p21 biosynthesis, Female, Mice, Mice, Inbred BALB C, Transcription, Genetic genetics, Tumor Cells, Cultured, Breast Neoplasms metabolism, Breast Neoplasms pathology, Cyclin-Dependent Kinase Inhibitor p21 genetics, Progestins pharmacology, Receptor, ErbB-2 metabolism, Receptors, Progesterone metabolism, STAT3 Transcription Factor metabolism, Transcription, Genetic drug effects
- Abstract
Cell cycle regulator p21(CIP1) has controversial biological effects in breast cancer since in spite of its role as cell cycle inhibitor and promoter of cellular senescence, it also induces cell proliferation and chemoteraphy resistance. We here explored the molecular mechanisms involved in progestin regulation of p21(CIP1) expression. We also investigated the biological effects of p21(CIP1) in breast cancer cells. We found that the synthetic progestin medroxyprogesterone acetate (MPA) upregulates p21(CIP1) protein expression via c-Src, signal transducer and activator of transcription 3 (Stat3) and ErbB-2 phosphorylation. Notably, we also found that ErbB-2 nuclear function plays a key role in MPA-induction of p21(CIP1) expression. Interestingly, we determined that progestin drives p21(CIP1) transcriptional activation via a novel nonclassical transcriptional mechanism in which progesterone receptor is recruited along with Stat3 and ErbB-2 to a Stat3 binding site at p21(CIP1) promoter. Our findings revealed that ErbB-2 functions as a coactivator of Stat3 in progestin induction of p21(CIP1) transcriptional activation. Furthermore, we demonstrated that blockage of p21(CIP1) expression strongly inhibited in vitro and in vivo progestin-induced breast cancer cell proliferation. These results further support the hypothesis that according to cell context and type of stimulus, p21(CIP1) is capable of inducing cell cycle progression. Moreover, we provided evidence that Stat3 and nuclear ErbB-2 are key players in progestin-induced p21(CIP1) regulation., (Copyright © 2012 Elsevier Inc. All rights reserved.)
- Published
- 2013
- Full Text
- View/download PDF
37. Constitutive HER2 signaling promotes breast cancer metastasis through cellular senescence.
- Author
-
Angelini PD, Zacarias Fluck MF, Pedersen K, Parra-Palau JL, Guiu M, Bernadó Morales C, Vicario R, Luque-García A, Navalpotro NP, Giralt J, Canals F, Gomis RR, Tabernero J, Baselga J, Villanueva J, and Arribas J
- Subjects
- Animals, Blotting, Western, Breast Neoplasms metabolism, Cell Line, Tumor, Enzyme-Linked Immunosorbent Assay, Female, Humans, Immunohistochemistry, Mice, Mice, Inbred BALB C, Microscopy, Confocal, Transplantation, Heterologous, Breast Neoplasms pathology, Cellular Senescence physiology, Receptor, ErbB-2 metabolism, Signal Transduction physiology
- Abstract
Senescence, a terminal cell proliferation arrest, can be triggered by oncogenes. Oncogene-induced senescence is classically considered a tumor defense barrier. However, several findings show that, under certain circumstances, senescent cells may favor tumor progression because of their secretory phenotype. Here, we show that the expression in different breast epithelial cell lines of p95HER2, a constitutively active fragment of the tyrosine kinase receptor HER2, results in either increased proliferation or senescence. In senescent cells, p95HER2 elicits a secretome enriched in proteases, cytokines, and growth factors. This secretory phenotype is not a mere consequence of the senescence status and requires continuous HER2 signaling to be maintained. Underscoring the functional relevance of the p95HER2-induced senescence secretome, we show that p95HER2-induced senescent cells promote metastasis in vivo in a non-cell-autonomous manner.
- Published
- 2013
- Full Text
- View/download PDF
38. Evaluation of fetal heart rate variation during amniocentesis: correlation with fetal karyotype.
- Author
-
Pietropolli A, Martelli F, Vicario R, Montagnoli C, Ticconi C, and Piccione E
- Subjects
- Female, Fetal Monitoring methods, Humans, Karyotyping methods, Pregnancy, Amniocentesis adverse effects, Fetus metabolism, Heart Rate, Fetal physiology
- Abstract
Objective: We monitored the fetal heart rate (FHR) during amniocentesis in fetuses at 16-18 weeks of gestation and investigated whether an abnormal FHR is associated with chromosomal abnormalities., Methods: This prospective study involves 807 women at 16-18 weeks of gestation who underwent genetic amniocentesis. The FHR, expressed as beats for minute, is recorded before (FHR1), immediately after (FHR2) and 60 min after (FHR3) the invasive procedure. Structural malformations detected by ultrasound and multiple pregnancy are excluded from the study., Results: Chromosomal abnormalities have been diagnosed in 27 fetuses. A mean FHR decrease after amniocentesis has been observed in normal and in abnormal fetuses. The mean variation during amniocentesis is significant in both groups (P < 0.01). The comparison between the mean FHR of the two groups shows no differences in FHR1 and FHR2 (P > 0.05) but a significant difference in FHR3 (P < 0.05)., Conclusion: The FHR decreases after amniocentesis; the decrease is larger in chromosomally abnormal fetuses than in normal fetuses. This difference in heart rate reaction to amniocentesis might be due to cardiac defects or developmental delay associated with the abnormal karyotype.
- Published
- 2011
- Full Text
- View/download PDF
39. Frontonasal facial angle in chromosomally normal fetuses at 11+0 to 13+6 weeks.
- Author
-
Vicario R, Pirollo LM, De Angelis C, Narcisi M, Pietropolli A, and Piccione E
- Subjects
- Adult, Crown-Rump Length, Down Syndrome diagnostic imaging, Female, Humans, Mass Screening, Nuchal Translucency Measurement, Pregnancy, Pregnancy Trimester, First, Prospective Studies, Reference Values, Face diagnostic imaging, Ultrasonography, Prenatal
- Abstract
Aim: To establish the normal range of frontonasal angle (FNA) at 11+0 to 13+6 weeks of gestation and the feasibility of FNA measurement, evaluate the correlation of such a parameter with crown-rump length (CRL) and nuchal translucency (NT) and assess the potential of FNA in improving the performance of first trimester sonographic and biochemical screening for trisomy 21., Methods: We conducted a prospective study in 400 singleton uncomplicated pregnancies. FNA was obtained during maternal screening for trisomy 21. NT thickness and FNA were measured by 2D ultrasound in a midsagittal plane of the fetal profile. FNA was measured between the line along the upper surface of the frontal bone and the superior edge of the nasal profile until the echogenic tip. Determination of maternal serum free β-human chorionic gonadotropin (β-hCG) and pregnancy-associated plasma protein-A (PAPP-A) was committed and concomitantly evaluated by blood sample. Patient-specific risk was calculated using Fetal Medicine Foundation software (Astraia Software GMBH, Munich, Germany)., Results: Mean FNA increased with CRL from 119.80° at CRL 45 mm to 125.85° at CRL 84 mm. A significant association between the FNA and NT thickness was detected, while no significant association was found between FNA and serum PAPP-A or β-hCG., Conclusion: At 11+0 to 13+6 weeks FNA increases with fetal CRL and NT thickness. Such an increase is not related to serum biochemistry., (© 2010 The Authors. Journal of Obstetrics and Gynaecology Research © 2010 Japan Society of Obstetrics and Gynecology.)
- Published
- 2010
- Full Text
- View/download PDF
40. Cutaneous vasculitis in a patient with acute brucellosis.
- Author
-
Franco Vicario R, Balparda J, Santamaria JM, Alvaro C, Arizaga C, de la Villa FM, Arrinda JM, Fernandez Moral R, and Celada A
- Subjects
- Adult, Female, Granuloma complications, Granuloma pathology, Humans, Purpura pathology, Skin pathology, Vasculitis, Leukocytoclastic, Cutaneous pathology, Brucellosis complications, Purpura complications, Vasculitis, Leukocytoclastic, Cutaneous complications
- Abstract
A patient suffering from brucellosis developed maculonodular and purpuric lesions. The skin biopsy showed granulomatous vasculitis with no deposition of immunoglobulins and complement on the vessels.
- Published
- 1985
- Full Text
- View/download PDF
41. Report of a case: acromesomelic dysplasia: radiologic, clinical, and pathological study.
- Author
-
Fernández del Moral R, Santolaya Jiménez JM, Rodríguez González JI, and Franco Vicario R
- Subjects
- Bone Diseases, Developmental complications, Consanguinity, Female, Humans, Middle Aged, Radiography, Skull diagnostic imaging, Syndrome, Bone Diseases, Developmental pathology, Dwarfism complications, Hydrocephalus complications, Intellectual Disability complications
- Abstract
We report a 51-year-old woman with acromesomelic dysplasia. Pathologic studies on adult bone are reported. Hydrocephalus and mild oligophrenia are additional findings.
- Published
- 1989
- Full Text
- View/download PDF
Catalog
Discovery Service for Jio Institute Digital Library
For full access to our library's resources, please sign in.