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Loss of HER2 in breast cancer: biological mechanisms and technical pitfalls

Cancer Drug Resistance 2022年第4期5卷 971-980页

作者： Stefania Morganti Mariia Ivanova emanuela ferraro Liliana Ascione Grazia Vivanet Giuseppina Bonizzi Giuseppe Curigliano Nicola Fusco Carmen Criscitiello Division of Early Drug Development for Innovative Therapies IEOEuropean Institute of Oncology IRCCSMilan 20144Italy Department of Oncology and Haemato-Oncology University of MilanoMilan 20122Italy Breast Oncology Center Dana-Farber Cancer InstituteBostonMA 02215USAHarvard Medical SchoolBostonMA 02215USA Biobank for Translational and Digital Medicine Unit IEOEuropean Institute of Oncology IRCCSMilan 20144Italy Division of Pathology IEOEuropean Institute of Oncology IRCCSMilan 20144Italy Breast Medicine Service Department of MedicineMemorial Sloan Kettering Cancer CenterNew YorkNY 10065USA.

Loss of HER2 in previously HER2-positive breast tumors is not rare, occurring in up to 50% of breast cancers;however, clinical research and practice underestimate this issue. Many studies have reported the loss of HER2 afterneoadjuvant therapy and at metastatic relapse and identified clinicopathological variables more frequentlyassociated with this event. Nevertheless, the biological mechanisms underlying HER2 loss are still poorlyunderstood. HER2 downregulation, intratumoral heterogeneity, clonal selection, and true subtype switch have beensuggested as potential causes of HER2 loss, but translational studies specifically investigating the biology behindHER2 loss are virtually absent. On the other side, technical pitfalls may justify HER2 loss in some of these samples.The best treatment strategy for patients with HER2 loss is currently unknown. Considering the prevalence of thisphenomenon and its apparent correlation with worse outcomes, we believe that correlative studies specificallyaddressing HER2 loss are warranted.

关键词： HER2 loss breast cancer subtype switch tumor heterogeneity clonal selection HER2 downregulation technical pitfalls

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Opportunities and challenges of implementing Pharmacogenomics in cancer drug development

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Cancer Drug Resistance 2019年第1期2卷 43-52页

作者： Paolo Tarantino Dario Trapani Stefania Morganti emanuela ferraro Giulia Viale Paolo D’Amico Bruno Achutti Duso Giuseppe Curigliano Division of Early Drug Development for Innovative Therapies IEOEuropean Institute of Oncology IRCCSMilan 20141Italy Department of Oncology and Haematology(DIPO) University of MilanMilan 20122Italy

Cancer drug development is a time and resources consuming process.Around 90%of drugs entering clinical trials fail due to lack of efficacy and/or safety issues,more often after conspicuous research and economic efforts.Part of the discarded drugs might be beneficial only in a subgroup of the study patients,and some adverse events might be prevented by identifying those patients more vulnerable to toxicities.The implementation of pharmacogenomic biomarkers allows the categorization of patients,to predict efficacy and toxicity and to optimize the drug development process.Around seventy FDA approved drugs currently present one or more genetic biomarker to keep in consideration,and with the progress of Precision Medicine tailoring therapies on individuals’genomic landscape promises to become a new standard of cancer care.In the current article we review the role of pharmacogenomics in cancer drug development,underlying the advantages and challenges of their implementation.

关键词： Pharmacogenomics cancer drug development precision medicine clinical trials

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Advancing computer-generated holographic display thanks to diffraction model-driven deep nets

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Opto-Electronic Advances 2024年第1期7卷 1-3页

作者： Vittorio Bianco Pietro ferraro CNR-ISASI Institute of Applied Sciences&Intelligent Systems Viale Campi Flegrei 3480078 Pozzuoli(Na)Italy

Advancements are reported in computer-generated holography proofing RGB 4K display through a new strategy based on diffraction model-driven deep networks. In the new 4K-DMDNet, the network is not a “black box” anymore. Rather, the input-output relation must obey to the physics of wavefront propagation, which is embedded here as a constraint. Thus, a labelled dataset is not required, and the model shows superior generalization capabilities with respect to data-driven approaches. The method is promising for the new generation of RGB 4K holographic display, as well as augmented and virtual reality systems.

关键词： holographic generalization constraint

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Percutaneous insertion of a novel dedicated metal stent to treat malignant hilar biliary obstruction

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World Journal of Gastrointestinal Oncology 2022年第9期14卷 1833-1843页

作者： Francesco Cortese Fabrizio Acquafredda Andrea Mardighian Maria Teresa Zurlo Valentina ferraro Riccardo Memeo Stavros Spiliopoulos Riccardo Inchingolo Interventional Radiology Unit Miulli HospitalAcquaviva Delle Fonti 70124Italy Unit of Hepatobiliary Surgery Miulli hospitalAcquaviva Delle Fonti 70124Italy 2nd Radiology Department National and Kapodistrian University of AthensChaidari Athens 12461Greece

BACKGROUND Percutaneous bilateral biliary stenting is an established method for the management of unresectable malignant hilar biliary obstruction.AIM To evaluate the efficacy and safety of a novel uncovered biliary stent, specifically designed for hilar reconstruction.METHODS This, single-center, retrospective study included 18 patients(mean age 71 ± 11 years;61.1% male) undergoing percutaneous transhepatic Moving cell stent(MCS) placement for hilar reconstruction using the stent-in-stent technique for malignant biliary strictures, between November 2020 and July 2021. The Patients were diagnosed with cholangiocarcinoma(12/18;66.6%), gallbladder cancer(5/18;27.7%), and colorectal liver metastasis(1/18;5.5%). Primary endpoints were technical(appropriate stent placement) and clinical(relief from jaundice) success. Secondary endpoints included stent patency, overall survival, complication rates and stent-related complications.RESULTS The technical and clinical success rates were 100%(18/18 cases). According to Kaplan-Meier analysis, the estimated overall patient survival was 80.5% and 60.4% at 6 and 12 mo respectively, while stent patency was 90.9% and 68.2% at 6 mo and 12 mo respectively. The mean stent patency was 172.53 ± 56.20 d and median stent patency was 165 d(range 83-315). Laboratory tests for cholestasis significantly improved after procedure: mean total bilirubin decreased from 15.2 ± 6.0 mg/d L to 1.3 ± 0.4 mg/d L(P < 0.001);mean γGT decreased from 1389 ± 832 U/L to 114.6 ± 53.5 U/L(P < 0.001). One periprocedural complication was reported. Stent-related complications were observed in 5 patients(27.7%), including 1 occlusion(5.5%) and 1 stent migration(5.5 %).CONCLUSION Percutaneous hilar bifurcation biliary stenting with the MCS resulted in excellent clinical and technical success rates, with acceptable complication rates. Further studies are needed to confirm these initial positive results.

关键词： Malignant hilar biliary obstructions Hilar cholangiocarcinoma Self-expandable metallic stent Stent-in-stent technique Percutaneous approach Bilateral Y-stenting

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Digital holography as metrology tool at micronanoscale for soft matter

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Light(Advanced Manufacturing) 2022年第1期3卷 128-153页

作者： Zhe Wang Lisa Miccio Sara Coppola Vittorio Bianco Pasquale Memmolo Volodymyr Tkachenko Vincenzo ferraro Ernesto Di Maio Pier Luca Maffettone Pietro ferraro CNR-ISASI Institute of Applied Sciences and Intelligent Systems"E.Caianiello"Via Campi Flegrei 3480078 PozzuoliNapoliItaly Dipartimento di Ingegneria Chimica dei Materiali e della Produzione Industriale Universitàdegli Studi di Napoli"Federico II"Piazzale Tecchio 8080125 NapoliItaly NEAPoLIS Numerical and Experimental Advanced Program on Liquids and Interface SystemsJoint Research Center CNR Universitàdegli Studi di Napoli"Federico II"NapoliItaly

The appearance of the first laser approximately 12 years after the invention of holography by Gabor(1948)revolutionized the field of optical metrology.In fact,the invention of holographic interferometry enabled the exploitation of interferometry on non-mirror surfaces and full-scale objects.The holography-based measurement methods has been implemented to several industrial systems or in support of R&D with the aim of improving new products in many fields(automotive,aerospace,electronics,etc.).To date,holography has been considered an important measurement tool for non-destructive inspection(NDI),strain-stress measurement,and vibration analysis at various engineering sites.Recently,the new paradigm of Industry4.0 has seen the introduction of new technologies and methods of processing materials as well as the development of manufacturing approaches for the realization of innovative products.For example,direct printing,additive,and bottom-up manufacturing processes are expected to involve new ways of making products in future,and most innovative fabrication processes will be based on the manipulation of soft matter(e.g.,starting from the liquid phase)that will be shaped at the nanoscale.The inherent characteristics of digital holography(DH)make it a powerful and accurate tool for the visualization and testing of final products,as well as for in situ and real-time monitoring and quantitative characterization of the processes involved during the fabrication cycle.This review aims to report on the most useful applications of soft matter,where the capabilities offered by DH,such as three-dimensional(3D)imaging,extended focus,3D tracking,full-field analysis,high sensitivity,and a wide range of measurements from nanometers to centimeters,permit completely non-invasive characterizations on a full-scale.Several holographic experimental results of typical samples are reported and discussed where DH plays a primary role as a tool gauge for soft matter.

关键词： Digital holography Soft matter Microscopy Thin film Polymers Liquids Characterization Interferometry Inkjet printing

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Overview of current detection methods and microRNA potential in Clostridioides difficile infection screening

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World Journal of Gastroenterology 2023年第22期29卷 3385-3399页

作者： Marco Bocchetti Maria Grazia ferraro Federica Melisi Piera Grisolia Marianna Scrima Alessia Maria Cossu Tung On Yau Department of Precision Medicine University of Campania“Luigi Vanvitelli”Naples 80138Italy Department of Molecular Oncology Precision Medicine Laboratory and COVID19 LaboratoryBiogem ScarlAriano Irpino 83031Italy School of Infection and Immunity College of Medical Veterinary and Life SciencesUniversity of GlasgowGlasgow G128QQUnited Kingdom Department of Pharmacy School of Medicine and SurgeryUniversity of Naples“Federico Ⅱ”Naples 80131Italy School of Science and Technology Nottingham Trent UniversityNottingham NG118NSUnited Kingdom Department of Rural Land Use Scotland’s Rural CollegeAberdeen AB219YAScotlandUnited Kingdom Department of Health Science University of the PeoplePasadenaCA 9110112United States

Clostridioides difficile(formerly called Clostridium difficile,C.difficile)infection(CDI)is listed as an urgent threat on the 2019 antibiotic resistance threats report in the United States by the Centers for Disease Control and Prevention.Early detection and appropriate disease management appear to be essential.Meanwhile,although the majority of cases are hospital-acquired CDI,community-acquired CDI cases are also on the rise,and this vulnerability is not limited to immunocompromised patients.Gastrointestinal treatments and/or gastrointestinal tract surgeries may be required for patients diagnosed with digestive diseases.Such treatments could suppress or interfere with the patient’s immune system and disrupt gut flora homeostasis,creating a suitable microecosystem for C.difficile overgrowth.Currently,stool-based non-invasive screening is the first-line approach to CDI diagnosis,but the accuracy is varied due to different clinical microbiology detection methods;therefore,improving reliability is clearly required.In this review,we briefly summarised the life cycle and toxicity of C.difficile,and we examined existing diagnostic approaches with an emphasis on novel biomarkers such as microRNAs.These biomarkers can be easily detected through noninvasive liquid biopsy and can yield crucial information about ongoing pathological phenomena,particularly in CDI.

关键词： Clostridioides difficile microRNA Diagnostic Prognostic Biomarker

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Microglia activation:a role for mitochondrial DNA?

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Neural Regeneration Research 2021年第12期16卷 2393-2394页

作者： Marcello Pinti Diana ferraro Milena Nasi Department of Life Sciences University of Modena and Reggio Emiliavia CampiModenaItaly Department of Neurosciences Azienda Ospedaliero-Universitaria di Modena Ospedale Civile di Baggiovaravia GiardiniBaggiovara(MO)Italy Department of Biomedical Metabolic and NeurosciencesUniversity of Modena and Reggio Emiliavia CampiModenaItaly Department of Surgery MedicineDentistry and Morphological SciencesUniversity of Modena and Reggio Emiliavia CampiModenaItaly

Microglial cells and perivascular macrophages are the only resident immune cells of the brain parenchyma and act as innate immune sentinels in the central nervous system(CNS).Microglial cells are vital for the maintenance of CNS homeostasis thanks to their strict interaction with neurons.When the homeostasis of the microenvironment is disrupted,microglia can alter their phenotype acquiring pro-or antiinflammatory function to defend the brain.

关键词： homeostasis activation strict

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Quantitative imaging of the complexity in liquid bubbles’evolution reveals the dynamics of film retraction

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Light(Science & Applications) 2019年第1期8卷 1021-1032页

作者： Biagio Mandracchia Zhe Wang Vincenzo ferraro Massimiliano Maria Villone Ernesto Di Maio Pier Luca Maffettone Pietro ferraro CNR-ISASI Istituto di Scienze Applicate e Sistemi Intelligenti“E.Caianiello”del CNRVia Campi Flegrei 3480078 PozzuoliNapoliItaly College of Applied Sciences Beijing University of Technology100124 BeijingChina Dipartimento di Ingegneria Chimica dei Materiali e della Produzione IndustrialeUniversita di Napoli FedericoⅡPiazzale Tecchio 8080125 NapoliItaly

The dynamics and stability of thin liquid films have fascinated scientists over many decades.Thin film flows are central to numerous areas of engineering,geophysics,and biophysics and occur over a wide range of lengths,velocities,and liquid property scales.In spite of many significant developments in this area,we still lack appropriate quantitative experimental tools with the spatial and temporal resolution necessary for a comprehensive study of film evolution.We propose tackling this problem with a holographic technique that combines quantitative phase imaging with a custom setup designed to form and manipulate bubbles.The results,gathered on a model aqueous polymeric solution,provide unparalleled insight into bubble dynamics through the combination of a full-field thickness estimation,threedimensional imaging,and a fast acquisition time.The unprecedented level of detail offered by the proposed methodology will promote a deeper understanding of the underlying physics of thin film dynamics.

关键词： film dynamics liquid

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Consequences of Helicobacter pylori infection in children

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World Journal of Gastroenterology 2010年第41期16卷 5181-5194页

作者： Lucia Pacifico Caterina Anania John F Osborn Flavia ferraro Claudio Chiesa Department of Pediatrics Sapienza University of Rome 324 I-00161 Rome Italy Department of Public Health Sciences Sapienza University of Rome I-00185 Rome Italy Department of Molecular Medicine National Research Council I-00133 Rome Italy

Although evidence is emerging that the prevalence of Helicobacter pylori (H. pylori) is declining in all age groups, the understanding of its disease spectrum continues to evolve. If untreated, H. pylori infection is lifelong. Although H. pylori typically colonizes the hu-man stomach for many decades without adverse con-sequences, children infected with H. pylori can manifest gastrointestinal diseases. Controversy persists regarding testing (and treating) for H. pylori infection in children with recurrent abdominal pain, chronic idiopathic thrombocytopenia, and poor growth. There is evidence of the role of H. pylori in childhood iron deficiency anemia, but the results are not conclusive. The possibility of an inverse relationship between H. pylori and gastroesophageal reflux disease, as well as childhood asthma, remains a controversial question. A better understanding of the H. pylori disease spectrum in childhood should lead to clearer recommendations about testing for and treating H. pylori infection in children who are more likely to develop clinical sequelae.

关键词： Helicobacter pylori Children Gastrointestinal diseases Epigastric pain Anemia Growth retardation Chronic idiopathic thrombocytopenic pupura

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Awake robotic liver surgery:A case report

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World Journal of Gastrointestinal Surgery 2023年第12期15卷 2954-2961页

作者： Antonella Delvecchio Gaetano Pavone Maria Conticchio Claudia Piacente Miriam Varvara Valentina ferraro Matteo Stasi Annachiara Casella Rosalinda Filippo Michele Tedeschi Carmine Pullano Riccardo Inchingolo Vito Delmonte Riccardo Memeo Unit of Hepato-Pancreatic-Biliary Surgery “F.Miulli”Regional General HospitalBari 70021Italy Unit of Anesthesia and Perioperative Medicine “F.Miulli”Regional General HospitalBari 70021Italy Villa Pia Hospital Rome 00151Italy Unit of Interventional Radiology “F.Miulli”Regional General HospitalBari 70021Italy

BACKGROUND In recent years,minimally invasive liver resection has become a standard of care for liver tumors.Considering the need to treat increasingly fragile patients,general anesthesia is sometimes avoided due to respiratory complications.Therefore,surgical treatment with curative intent is abandoned in favor of a less invasive and less radical approach.Epidural anesthesia has been shown to reduce respiratory complications,especially in elderly patients with pre-existing lung disease.CASE SUMMARY A 77-year-old man with hepatitis-C-virus-related chronic liver disease underwent robotic liver resection for hepatocellular carcinoma.The patient was suffering from hypertension,diabetes and chronic obstructive pulmonary disease.The National Surgical Quality Improvement Program score for developing pneumonia was 9.2%.We planned a combined spinal–epidural anesthesia with conscious sedation to avoid general anesthesia.No modification of the standard surgical technique was necessary.Hemodynamics were stable and bleeding was minimal.The postoperative course was uneventful.CONCLUSION Robotic surgery in locoregional anesthesia with conscious sedation could be considered a safe and suitable approach in specialized centers and in selected patients.

关键词： Robotic surgery Awake surgery Liver resection Frail patient Locoregional anesthesia Conscious sedation Case report

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