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Chemotherapy for Hepatocellular Carcinoma: Current Evidence and Future Perspectives

Journal of Clinical and Translational Hepatology 2017年第3期5卷 235-248页

作者： Emanuele Rinninella Lucia Cerrito irene spinelli Marco Cintoni Maria Cristina Mele Maurizio Pompili Antonio Gasbarrini Internal Medicine and Gastroenterology Unit Gastroenterology Area Fondazione Policlinico Universitario Agostino GemelliCatholic University of Sacred Heart Rome Italy Clinical Nutrition Unit Gastroenterology Area Fondazione Policlinico Universitario Agostino Gemelli Catholic University of Sacred Heart Rome Italy Internal Medicine and Gastroenterology Unit Gastroenterology Area Fondazione Policlinico Universitario Agostino GemelliCatholic University of Sacred Heart Rome Italy Clinical Nutrition Unit Gastroenterology Area Fondazione Policlinico Universitario Agostino Gemelli Catholic University of Sacred Heart Rome Italy

Hepatocarcinogenesis is a multistep process,heralded by abnormalities in cell differentiation and proliferation and sustained by an aberrant *** the underlying molecular pathogenesis leading to hepatocellular carcinoma is a prerequisite to develop new drugs that will hamper or block the steps of these *** hepatocellular carcinoma has higher arterial vascularization than normal liver,this could be a good target for novel molecular *** of the antiangiogenic drug sorafenib into clinical practice since 2008 has led to new perspectives in the management of this *** importance of this drug lies not only in the modest gain of patients' survival,but in having opened a roadmap towards the development of new molecules and ***,after the introduction of sorafenib,during the last years,a wide number of clinical trials on antiangiogenic therapies failed in achieving significant ***,many of these trials are still ongoing and promise to improve overall survival and progression-free survival.A recent clinical trial has proven regorafenib effective in patients showing tumor progression under sorafenib,thus opening new interesting therapeutic *** other expectations have been borne from the discovery of the immune checkpoint blockade,already known in other solid ***,a potential role in hepatocellular carcinoma therapy may derive from the use of branched-chain amino acids and of nutritional *** review analyses the biomolecular pathways of hepatocellular carcinoma and the ongoing studies,the actual evidence and the future perspectives concerning drug therapy in this open field.

关键词： Hepatocellular carcinoma Molecular target therapies Immunotherapy Branched-chain amino acids

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Reverse time-dependent effect of alphafetoprotein and disease control on survival of patients with Barcelona Clinic Liver Cancer stage C hepatocellular carcinoma

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World Journal of Hepatology 2017年第36期9卷 1322-1331页

作者： Francesca Romana Ponziani irene spinelli Emanuele Rinninella Lucia Cerrito Antonio Saviano Alfonso Wolfango Avolio Michele Basso Luca Miele Laura Riccardi Maria Assunta Zocco Brigida Eleonora Annicchiarico Matteo Garcovich Marco Biolato Giuseppe Marrone Anna Maria De Gaetano Roberto Iezzi Felice Giuliante Fabio Maria Vecchio Salvatore Agnes Giovanni Addolorato Massimo Siciliano Gian Lodovico Rapaccini Antonio Grieco Antonio Gasbarrini Maurizio Pompili Department of Internal Medicine Gastroenterology and Hepatology Agostino Gemelli Hospital Department of Liver Transplant Surgery Agostino Gemelli Hospital Department of Oncology Gastroenterology and Hepatology Agostino Gemelli Hospital Department of Bioimaging and Radiological Sciences Agostino Gemelli Hospital Department of Hepatobiliary Surgery Agostino Gemelli Hospital Department of Pathology Agostino Gemelli Hospital

AIM To characterize the survival of cirrhotic patients with Barcelona Clinic Liver Cancer(BCLC) stage C hepatocellular carcinoma(HCC) and to ascertain the factors predicting the achievement of disease control(DC).METHODS The cirrhotic patients with BCLC stage C HCC evaluated by the Hepatocatt multidisciplinary group were subjected to the investigation. Demographic, clinical and tumor features, along with the best tumor response and overall survival were recorded. RESULTS One hundred and ten BCLC stage C patients were included in the analysis; the median overall survival was 13.4 mo(95%CI: 10.6-17.0). Only alphafetoprotein(AFP) serum level > 200 ng/m L and DC could independently predict survival but in a time dependent manner, the former was significantly associated with increased risk of mortality within the first 6 mo of follow-up(HR = 5.073, 95%CI: 2.159-11.916, P = 0.0002), whereas the latter showed a protective effect against death after one year(HR = 0.110, 95%CI: 0.038-0.314, P < 0.0001). Only patients showing microvascular invasion and/or extrahepatic spread recorded lower chances of achieving DC(OR = 0.263, 95%CI: 0.111-0.622, P = 0.002).CONCLUSION The BCLC stage C HCC includes a wide heterogeneous group of cirrhotic patients suitable for potentially curative treatments. The reverse and time dependent effect of AFP serum level and DC on patients' survival confers them as useful predictive tools for treatment management and clinical decisions.

关键词： Hepatocellular carcinoma Cirrhosis Barcelona Clinic Liver Cancer stage C Alphafetoprotein Disease control Performance status Survival

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Reassessing the AMPK-MTORC1 balance in autophagy in the central nervous system

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Neural Regeneration Research 2025年第11期20卷 3209-3210页

作者： Marta García-Juan Mario Villa irene Benito-Cuesta Lara Ordónez-Gutiérrez Francisco Wandosell Centro de Biología Molecular“Severo Ochoa”(CSIC-UAM) Nicolas Cabrera 1Universidad Autónoma de MadridMadridSpain Fisiología Animal Departamento de BiologíaFacultad de CienciasUniversidad Autónoma de MadridMadridSpain Department of Clinical Neuroscience CMM Karolinska Universitetssjukhuset SolnaStockholmSweden Departamento de Bioquímica y Biología Molecular Universidad Complutense de MadridMadridSpain Centro de Investigación Biomédica en Red de Enfermedades Neurodegenerativas(CIBERNED) MadridSpain

Autophagy is a cellular degradation and recycling system,indispensable for cellular and organ development,homeostasis,and *** cellular process is evolutionarily highly conserved to quality control of many proteins and dysfunctional organelles,which finally recycle components as amino *** process is effective during normal physiology as part of anabolism and plays an additional important role during starvation(Dikic and Elazar,2018).Different types of autophagy have been chara cterized based on their dynamic,mechanism of action,target substrates,and protein *** of them are macroautophagy(hereafter called"autophagy"),microa utophagy,and chape rone-media ted autophagy(Fleming et al.,2022).

关键词： homeostasis system hereafter

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Pathways of flower infection and pollen-mediated dispersion of Pseudomonas syringae pv. actinidiae, the causal agent of kiwifruit bacterial canker

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Horticulture Research 2018年第1期5卷 115-127页

作者： irene Donati Antonio Cellini Giampaolo Buriani Sofia Mauri Callum Kay Gianni Tacconi Francesco spinelli Department of Agricultural and Food Sciences-DISTAL Alma Mater Studiorum—University of Bolognaviale Fanin 4440127BolognaItaly ZESPRI GLOBAL Supply 400 Maunganui RoadMount MaunganuiNew Zealand Consiglio per la Ricerca e la Sperimentazione in Agricoltura—Genomics Research Centre via S.Protaso 30229017Fiorenzuola d’ArdaItaly

Flowers can provide a protected and nutrient-rich environment to the epiphytic microflora,thus representing a sensible entry point for pathogens such as Pseudomonas syringae ***(Psa).This bacterium can colonize both male and female Actinidia flowers,causing flower browning and fall,and systemic invasion of the host plant,eventually leading to its ***,the process of flower colonization and penetration into the host tissues has not yet been fully *** addition,the presence of Psa in the pollen from infected flowers,and the role of pollination in the spread of Psa requires *** present study employed a Psa strain constitutively expressing the fluorescent GFPuv protein,to visualize in vivo flower *** observations were performed by means of confocal laser scanning and wide-field fluorescent microscopy,and were coupled with the study of Psa population dynamics by quantitative PCR(q-PCR).The pathogen was shown to colonize stigmata,move along the stylar furrow,and penetrate the receptacles via the style or *** the receptacle was invaded,the pathogen migrated along the flower pedicel and became *** was also able to colonize the anthers epiphytically and *** male flowers produced contaminated pollen,which could transmit Psa to healthy ***,pollinators(Apis mellifera and Bombus terrestris)were studied in natural conditions,showing that,although they can be contaminated with Psa,the pathogen’s transmission via pollinators is contrasted by its short survival in the hive.

关键词： flowers eventually flower

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Liver collision lesion:inflammatory hepatocellular adenoma within focal nodular hyperplasia

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Gastroenterology Report 2021年第4期9卷 374-376,I0003页

作者： Matteo Renzulli irene Pettinari Francesco Vasuri Matteo Ravaioli Beniamino Corcioni Daniele spinelli Giovanni Marasco Matteo Cescon Antonietta D’Errico Rita Golfieri Department of Radiology IRCCS Azienda Ospedaliero-Universitaria di BolognaVia Albertoni 15BolognaItalia Pathology Unit S.Orsola Malpighi University HospitalBolognaItaly General Surgery and Transplantation Unit Department of Medical and Surgical SciencesS.Orsola HospitalUniversity of BolognaBolognaItaly Department of Medical and Surgical Sciences S.Orsola HospitalUniversity of BolognaBolognaItaly

Introduction Focal nodular hyperplasia(FNH)and hepatocellular adenoma(HCA)are both benign nodular hepatocellular *** is the second-most common solid liver tumour,representing8%of all primary hepatic neoplasms[1].If the diagnosis of FNH is firmly established on the basis of imaging,and if the individual is asymptomatic,follow-up imaging is not required,and the patient can be ***,there is a poor association between FNH and symptoms;therefore,even in symptomatic cases,treatment is rarely indicated[2].

关键词：局灶性结节增生 neoplasms diagnosis 肝细胞

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Past,present and future of industrial plantation forestry and implication on future timber harvesting technology

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Journal of Forestry Research 2020年第2期31卷 339-351页

作者： Andrew McEwan Enrico Marchi Raffaele spinelli Michal Brink Department of Agriculture Food and Forest SystemsFlorence UniversityVia San Bonaventura1350145 FlorenceItaly School of Natural Resource Management Nelson Mandela Metropolitan UniversityGeorge CampusGeorgeSouth Africa Consiglio Nazionale delle Ricerche Istituto per la BioEconomiaVia Madonna del Piano 10Sesto FiorentinoItaly Australian Forest Operations Research Alliance University of the Sunshine CoastLocked Bag 4Maroochydore DCQLD 4558Australia University of Pretoria Private Bag X20HatfieldPretoria 0028South Africa

Plantation forests are established,and expanding,to satisfy increasing global demand for timber *** societal values,such as safety,productivity,environmental,quality and social are influencing the plantation forestry *** is primarily driven through an ever increasing world population,which in turn influences the way nations view the value systems by which they *** people require more resources-also forest ***,the availability of information is influencing the pace of technological *** changes could result in a difference in the management of plantations that could affect the forest engineering systems of the *** review aimed to summarize the current status of plantation forests;summarize future developments and possible scenarios in forest plantation management for the various products;and assess whether these developments in a plantation environment could affect the harvesting systems *** influencing the form of plantations include the type and nature of the plantation owner;the change in demand for different and new forest products;climate change factors,including the use of biomass for energy,carbon sequestration and trading;ecosystem services and other products and services;and sustainability certification of forest *** impact and influence of these factors were summarised into a series of key drivers that will influence the technology used in harvesting machines,as well as the choice of harvesting machines,systems and *** drivers were the effect of variations in tree size,the expansion of plantation areas onto more difficult terrain,diversity in plantation design,increased attention towards site impacts and the increased use of biomass for *** information is provided regarding how the harvesting systems could be affected.

关键词： Plantations Forest products Biomass Harvesting system Mechanization Trends Technology

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A Novel Intermediary Framework for Dynamic Edge Service Composition

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Journal of Computer Science & Technology 2012年第2期27卷 281-297页

作者： Claudia Canali Michele Colajanni Delfina Malandrino Vittorio Scarano Raffaele spinelli Department of Information Engineering University of Modena and Reggio Emilia Department of Computer Science University of Salerno

Multimedia content,user mobility and heterogeneous client devices require novel systems that are able to support ubiquitous access to the Web *** this scenario,solutions that combine flexibility,efficiency and scalability in offering edge services for ubiquitous access are *** propose an original intermediary framework,namely Scalable Intermediary Software Infrastructure （SISI）,which is able to dynamically compose edge services on the basis of user preferences and device *** SISI framework exploits a per-user profiling mechanism,where each user can initially set his/her personal preferences through a simple Web interface,and the system is then able to compose at run-time the necessary *** basic framework can be enriched through new edge services that can be easily implemented through a programming model based on APIs and internal *** experiments demonstrate that flexibility and edge service composition do not affect the system *** show that this framework is able to chain multiple edge services and to guarantee stable performance.

关键词： ubiquitous Web edge service intermediary framework service flow performance

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Microstructural Morphologies and Experimental Growth Laws during Solidification of Monotectic and Hypermonotectic Al-Pb Alloys

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Journal of Materials Science & Technology 2014年第4期30卷 401-407页

作者： Adrina P.Silva Amauri Garcia José E.spinelli Department of Materials Engineering University of Campinas-UNICAMP Department of Materials Engineering Federal University of Sao Carlos-UFSCar

AI-Pb alloys with monotectic and hypermonotectic compositions were directionally solidified under unsteady- state heat flow conditions. The cooling curves recorded during solidification allowed solidification thermal parameters such as the cooling rate （T）, growth rate （v） and thermal gradient （G） to be experimentally determined. Different microstructural patterns have been associated with the alloy solute content, i.e., AI-1.2 and 2.1 wt% Pb. A sequence of morphologies from the bottom to the top of the A1-1.2 wt% Pb alloy casting （monotectic） can be observed： Pb-rich droplets in the aluminum-rich matrix, followed by a region of microstructural transition formed by droplets and fibers and finally by a mixture of fibers and strings of pearls. A completely fibrous structure （without transition） has been observed along the entire AI-2.1 wt% Pb alloy casting （hypermonotectic）. The interphase spacing （λ） was measured along the casting length, and experimental correlations between λand experimental solidification thermal parameters have been established. Power laws with a -2.2 exponent expressing λ as a function of the growth rate, v, were found to better represent the fibrous growth of both AI-Pb alloys. Moreover, a single experimental law expressing λ as a function of both G and v was found to describe the fibrous growth of both the monotectic and the hypermonotectic alloys experimentally examined.

关键词： Aluminum alloys Casting Phase transformation

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Osmoprotectants and Antioxidative Enzymes as Screening Tools for Salinity Tolerance in Radish (Raphanus sativus)

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Horticultural Plant Journal 2020年第1期6卷 14-24页

作者： Rabab Sanoubar Antonio Cellini Giuseppe Gianfranco Francesco spinelli Department of Agricultural Sciences (DIPSA) University of Bologna

The research addresses the identification of a screening methodology for salt stress tolerance in radish cultivars. In the first experiment, two different radish cultivars(long white and round red) were compared in their morphological and physiological responses to different salinity levels. Round red radish showed better morphological and physiological responses to incremental salinity in terms of yield and better adaptation of overall water relations. In the second experiment, the most tolerant genotype from the first experiment was used as a control against other seven round red radish genotypes ranked by their salinity tolerance according to morphological, physiological and biochemical indices. Salt stress did not significantly affect malondialdehyde(MDA) and hydrogen peroxide(H2O2) content, and ascorbate peroxidase(APX) activity in the studied cultivars. Nonetheless, the relatively salt tolerant cultivar SAXA2 showed higher ability to accumulate compatible solutes(*** and proteins) and maintain osmotic adjustment. In addition, cultivar SAXA2 also showed considerable increase in glutathione reductase(GR) activity. Our results supported that accumulation of proline and higher GR activity are associated with radish salt tolerance, whereas no relationship with salinity was observed in superoxide dismutase(SOD), MDA and H2O2 content.

关键词： radish salt stress oxidative stress secondary metabolite antioxidant enzyme

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Exploring the silvicultural and economic viability of gap cutting in Mediterranean softwood plantations

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Forestry Studies in China 2012年第1期14卷 63-69页

作者： Roberto MERCURIO Raffaele spinelli Department of Agricultural and Forest Systems Management Mediterranean UniversityFeo di Vito89122 Reggio CalabriaItaly CNR IVALSA Via Madonna del Piano 10Sesto Fiorentino (FI)Italy

Gap cutting consists of the removal of all trees growing on a small surface, varying in size from 200 to 600 m2. In Italy, gap cutting has been successfully tested for introducing the natural regeneration of native species into softwood plantations, thus ac- celerating the transition towards climax hardwood stands. Depending on plantation types and conditions, gap cutting should be start- ed at an age between 70 and 80 years and the system should include at least 12 to 15 gaps, in order to produce enough wood to cover costs. Generally, natural regeneration is firmly established within 5-7 years from treatment. Gap cutting also offers superior results to selection thinning, the latter producing about 35% less value and incurring 25% to 30% more costs. As for all regeneration cuts, the success of gap cutting depends on wildlife control in order to prevent extensive damage to the regeneration.

关键词： gap cutting regeneration plantations economics technology

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