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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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The use of liquid biopsy in early breast cancer:clinical evidence and future perspectives

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Journal of Cancer Metastasis and Treatment 2021年第1期7卷 33-48页

作者： Paolo D’Amico Carla Corvaja Lorenzo Gerratana Carolina Reduzzi giuseppe curigliano Massimo Cristofanilli Division of Hematology and Oncology Department of MedicineNorthwestern University Feinberg School of MedicineChicagoIL 60611USA Division of Early Drug Development for Innovative Therapies IEOEuropean Institute of Oncology IRCCSMilan 20132Italy Department of Oncology and Hemato-Oncology University of MilanoMilan 20122Italy Department of Oncology ASUFCUniversity Hospital of UdineUdine 33100Italy Department of Medicine University of UdineUdine 33100Italy Department of Medical Oncology Centro di Riferimento Oncologico(CRO)IRCCSPordenone 33081Italy

Liquid biopsy,including both circulating tumor cells and circulating tumor DNA,is gaining momentum as a diagnostic modality adopted in the clinical management of breast cancer.Prospective studies testing several technologies demonstrated clinical validity and,in some cases,achieved the United States Food and Drug Administration approval.The initial testing and clinical application of liquid biopsy focused primarily on the diagnosis,while molecular characterization and monitoring of metastatic disease,with larger data from prospective studies,came in the last two decades.Although its role in metastatic setting is thus widely recognized,the current evidence does not provide support for the routine clinical use of liquid biopsy methods for the earlier stage of this disease.Considering the relevance of early detection,characterization,and management of breast cancer in the early-stage,this clinical setting is the most suitable to increase the chances for effective treatment selection and improved prognosis,and a better understanding of the main application of liquid biopsy tools in the earlier stage of breast cancer is therefore crucial.The aim of this review is to provide an overview of the clinical evidence and subsequent potential applications of liquid biopsy in early breast cancer,identifying the main existing caveats and the possible future scenarios.

关键词： Liquid biopsy early breast cancer circulating tumor cells circulating tumor DNA clinical trials screening early detection minimal residual disease

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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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How to identify early complications in patients undergoing distal gastrectomy?

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World Journal of Gastrointestinal Surgery 2024年第4期16卷 974-981页

作者： giuseppe Tropeano Maria Michela Chiarello Valeria Fico giuseppe Brisinda Emergency Surgery and Trauma Center Fondazione Policlinico Universitario A Gemelli IRCCSRome 00168Italy Department of Surgery Azienda Sanitaria Provinciale di CosenzaCosenza 87100Italy Department of Medical and Surgical Sciences UniversitàCattolica del Sacro CuoreRome 00168Italy

In this editorial we comment on the article by Zhang et al published in a recent issue of the World Journal of Gastrointestinal Surgery.Gastrectomy with appropriate lymph node dissection is still standard curative treatment in locally advanced gastric cancer.Several studies point out that gastric cancer surgery is a complex procedure that leads to a high risk of morbidity and mortality.Many factors can contribute to the onset of complications with consequent effects on prognosis and increased mortality.The complications can be divided in complications related to anastomosis,to motility and to surgical site infection.The study presented by Zhang B et al represent an interesting analysis on the possibility to prevent postoperative morbidity.The study was performed on 131 patients with distal gastric cancer who underwent gastrectomy with D2 lymph node dissection.Of these patients,16%developed early postoperative complications.The univariate analysis showed that prealbumin level,hypertension,diabetes,history of abdominal surgery,R0 resection,and blood transfusion were factors influencing early postoperative complications after distal gastrectomy.Moreover,the inclusion of the above significant variables in the logistic regression analysis revealed that hypertension,diabetes,a history of abdominal surgery,and blood transfusion were independent predictors of postoperative complications.In conclusion,preoperative and intraoperative factors can be used to establish an early postoperative nomogram model.The results of the study presented by Zhang et al suggest that the prediction model can be used to guide the detection of postoperative complications and has clinical reference value.

关键词： Gastric cancer Gastrectomy Lymph node dissection Morbidity Mortality Surgical site infections

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Autonomous Vehicle Platoons In Urban Road Networks:A Joint Distributed Reinforcement Learning and Model Predictive Control Approach

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IEEE/CAA Journal of Automatica Sinica 2024年第1期11卷 141-156页

作者： Luigi D’Alfonso Francesco Giannini giuseppe Franzè giuseppe Fedele Francesco Pupo Giancarlo Fortino IEEE the Department of Computer Engineering ModelingElectronics and SystemsUniversitàdella CalabriaVia Pietro BucciCubo 42-CRende(CS)87036Italy the Department of Mechanical Engineering Energy Engineering and ManagementUniversitàdella CalabriaVia Pietro BucciCubo 42-CRende(CS)87036Italy

In this paper, platoons of autonomous vehicles operating in urban road networks are considered. From a methodological point of view, the problem of interest consists of formally characterizing vehicle state trajectory tubes by means of routing decisions complying with traffic congestion criteria. To this end, a novel distributed control architecture is conceived by taking advantage of two methodologies: deep reinforcement learning and model predictive control. On one hand, the routing decisions are obtained by using a distributed reinforcement learning algorithm that exploits available traffic data at each road junction. On the other hand, a bank of model predictive controllers is in charge of computing the more adequate control action for each involved vehicle. Such tasks are here combined into a single framework:the deep reinforcement learning output(action) is translated into a set-point to be tracked by the model predictive controller;conversely, the current vehicle position, resulting from the application of the control move, is exploited by the deep reinforcement learning unit for improving its reliability. The main novelty of the proposed solution lies in its hybrid nature: on one hand it fully exploits deep reinforcement learning capabilities for decisionmaking purposes;on the other hand, time-varying hard constraints are always satisfied during the dynamical platoon evolution imposed by the computed routing decisions. To efficiently evaluate the performance of the proposed control architecture, a co-design procedure, involving the SUMO and MATLAB platforms, is implemented so that complex operating environments can be used, and the information coming from road maps(links,junctions, obstacles, semaphores, etc.) and vehicle state trajectories can be shared and exchanged. Finally by considering as operating scenario a real entire city block and a platoon of eleven vehicles described by double-integrator models, several simulations have been performed with the aim to put in light the main f eatures of the pro

关键词： Distributed model predictive control distributed reinforcement learning routing decisions urban road networks

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Climate change impacts on eutrophication in the Po River(Italy):Temperature-mediated reduction in nitrogen export but no effect on phosphorus

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Journal of Environmental Sciences 2024年第9期143卷 148-163页

作者： Elisa Soana Maria Pia Gervasio Tommaso Granata Daniela Colombo giuseppe Castaldelli Department of Environmental and Prevention Sciences University of FerraraVia Luigi Borsari 4644121 FerraraItaly CESI-Italian Electrical and Technical Experimental Center via Rubattino 5420134MilanoItaly

Rivers worldwide are under stress from eutrophication and nitrate pollution,but the ecological consequences overlap with climate change,and the resulting interactions may be unexpected and still unexplored.The Po River basin(northern Italy)is one of the most agriculturally productive and densely populated areas in Europe.It remains unclear whether the climate change impacts on the thermal and hydrological regimes are already affecting nutrient dynamics and transport to coastal areas.The present work addresses the long-term trends(1992-2020)of nitrogen and phosphorus export by investigating both the annual magnitude and the seasonal patterns and their relationship with water temperature and discharge trajectories.Despite the constant diffuse and point sources in the basin,a marked decrease(-20%)in nitrogen export,mostly as nitrate,was recorded in the last decade compared to the 1990 s,while no significant downward trend was observed for phosphorus.The water temperature of the Po River has warmed,with the most pronounced signals in summer(+0.13℃/year)and autumn(+0.16℃/year),together with the strongest increase in the number of warm days(+70%-80%).An extended seasonal window of warm temperatures and the persistence of low flow periods are likely to create favorable conditions for permanent nitrate removal via denitrification,resulting in a lower delivery of reactive nitrogen to the sea.The present results show that climate change-driven warming may enhance nitrogen processing by increasing respiratory river metabolism,thereby reducing export from spring to early autumn,when the risk of eutrophication in coastal zones is higher.

关键词： Nutrient export Eutrophication Climate change Water temperature Denitrification Po River

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Artificial intelligence in detection of small bowel lesions and their bleeding risk:A new step forward

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World Journal of Gastroenterology 2024年第18期30卷 2482-2484页

作者： Silvia Cocca Giuseppina Pontillo giuseppe Grande Rita Conigliaro Gastroenterology and Endoscopy Unit Azienda Ospedaliero Universitaria Policlinico di ModenaModena 41121Italy Gastroenterology and Endoscopy Unit Presidio Ospedaliero San Giuseppe Moscati(AversaCE)-ASL CasertaCaserta 81100Italy Department of Gastroenterology and Digestive Endoscopy Azienda Ospedaliero Universitaria di ModenaModena 41121Italy

The present letter to the editor is related to the study with the title“Automatic detection of small bowel(SB)lesions with different bleeding risk based on deep learning models”.Capsule endoscopy(CE)is the main tool to assess SB diseases but it is a time-consuming procedure with a significant error rate.The development of artificial intelligence(AI)in CE could simplify physicians’tasks.The novel deep learning model by Zhang et al seems to be able to identify various SB lesions and their bleeding risk,and it could pave the way to next perspective studies to better enhance the diagnostic support of AI in the detection of different types of SB lesions in clinical practice.

关键词： Capsule endoscopy Small bowel Artificial intelligence Bleeding risk Vascular lesions

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Planning of DC Electric Spring with Particle Swarm Optimization and Elitist Non-dominated Sorting Genetic Algorithm

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CSEE Journal of Power and Energy Systems 2024年第2期10卷 574-583页

作者： Qingsong Wang Siwei Li Hao Ding Ming Cheng giuseppe Buja School of Electrical Engineering and Jiangsu Provincial Key Laboratory of Smart Grid Technology and Equipment Southeast UniversityNanjing 210096China School of Software Engineering Southeast universitySuzhou 215123China

This paper addresses the planning problem of parallel DC electric springs (DCESs). DCES, a demand-side management method, realizes automatic matching of power consumption and power generation by adjusting non-critical load (NCL) and internal storage. It can offer higher power quality to critical load (CL), reduce power imbalance and relieve pressure on energy storage systems (RESs). In this paper, a planning method for parallel DCESs is proposed to maximize stability gain, economic benefits, and penetration of RESs. The planning model is a master optimization with sub-optimization to highlight the priority of objectives. Master optimization is used to improve stability of the network, and sub-optimization aims to improve economic benefit and allowable penetration of RESs. This issue is a multivariable nonlinear mixed integer problem, requiring huge calculations by using common solvers. Therefore, particle Swarm optimization (PSO) and Elitist non-dominated sorting genetic algorithm (NSGA-II) were used to solve this model. Considering uncertainty of RESs, this paper verifies effectiveness of the proposed planning method on IEEE 33-bus system based on deterministic scenarios obtained by scenario analysis.

关键词： DC distribution network DC electric spring non-dominated sorting genetic algorithm particle swarm optimization renewable energy source

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Keep in mind sex differences when prescribing psychotropic drugs

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World Journal of Psychiatry 2024年第2期14卷 194-198页

作者： Marianna Mazza Domenico De Berardis giuseppe Marano Department of Neurosciences Fondazione Policlinico Universitario A Gemelli IRCCSUniversitàCattolica del Sacro CuoreRome 00168Italy Mental Health NHSASL 4 TeramoTeramo 64100Italy

Women represent the majority of patients with psychiatric diagnoses and also the largest users of psychotropic drugs.There are inevitable differences in efficacy,side effects and long-term treatment response between men and women.Psychopharmacological research needs to develop adequately powered animal and human trials aimed to consider pharmacokinetics and pharmacodynamics of central nervous system drugs in both male and female subjects.Healthcare professionals have the responsibility to prescribe sex-specific psychopharmacotherapies with a priority to differentiate between men and women in order to minimize adverse drugs reactions,to maximize therapeutic effectiveness and to provide personalized management of care.

关键词： Women Psychopharmacology Psychotropic drugs Sex differences

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A novel 2D-GO@WS2 electrochemical platform for the determination of thiram fungicide

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Journal of Environmental Sciences 2024年第2期136卷 226-236页

作者： Khouloud Abid Daniela Iannazzo Consuelo Celesti Amani Khaskhoussi Antonino Foti Ramzi Maalej Pietro giuseppe Gucciardi Giovanni Neri Department of Engineering University of MessinaC.da Di DioI-98166 MessinaItaly INSTM Research Unity of MessinaItaly Laboratory of Dielectric and Photonic Materials Faculty of Sciences of SfaxSfaxUniversitySfax 3018Tunisia CNR IPCF Istituto per i Processi Chimico-Fisici viale F.Stagno D’Alcontres 37I-98156 MessinaItaly

In this paper,the determination of Thiram fungicide by a novel modified screen-printed carbon electrode(SPCE)fabricated modifying the working electrode(WE)with 2D-GO/WS2nanohybrid composites,is reported.Scanning electron microscopy(SEM),Raman spectroscopy,and fluorescence analysis(PL)were used to reveal the morphological and microstructural characteristics of the 2D-GO/WS2 nanohybrids with different graphene oxide:tungsten disulphide(GO:WS_(2))ratio.Electrochemical characterization demonstrated that the 2D-WS2/GO nanohybrids having a GO:WS_(2)ratio=2:1 shows the highest electrocatalytic activity towards oxidation of Thiram.The developed sensor permits the quantification of Thiram in the linear range 0.083-0.33μM with a limit of detection(LOD)of 0.02μM,which is below the legal limits for this fungicide in drinking water or foods.

关键词： WS_(2)nanosheets Graphene Oxide(GO) Electrochemical sensor Fungicides Thiram

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