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FOLFIRINOX and translational studies: Towards personalized therapy in pancreatic cancer

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World Journal of Gastroenterology 2016年第31期22卷 6987-7005页

作者： Chiara Caparello Laura L Meijer Ingrid Garajova Alfredo Falcone Tessa Y Le Large Niccola Funel Geert Kazemier Godefridus J Peters Enrico Vasile Elisa Giovannetti University Hospital of Pisa 56124 Pisa Italy Department of Medical Oncology VU University Medical Center 1081 HV Amsterdam The Netherlands Department of Surgery VU University Medical Center 1081 HV Amsterdam The Netherlands Department of Experimental Diagnostic and Speciality Medicine University of Bologna Sant'Orsola-Malpighi Hospital Via Massarenti 9 40138 Bologna Italy Cancer Pharmacology lab AIRC Start-Up Unit University of Pisa 56124 Pisa Italy CNR-Nano Institute of Nanoscience and Nanotechnology University of Pisa 56124 Pisa Italy

Pancreatic cancer is an extremely aggressive disease; although progress has been made in the last few years, the prognosis of these patients remains dismal. FOLFIRINOX is now considered a standard treatment in first-line setting, since it demonstrated an improved overall and progression-free survival vs gemcitabine alone. However, the enthusiasm over the benefit of this three-drug regimen is tempered by the associated increased toxicity profile, and many efforts have been made to improve the feasibility of this schedule. After a more recent phase Ⅲ trial showing an improved outcome over gemcitabine, the combination of gemcitabine/nab-paclitaxel emerged as another standard first-line treatment. However, this treatment is also associated with more side effects. In addition, despite initial promising data on the predictive role of SPARClevels, recent studies showed that these levels are not associated with nab-paclitaxel efficacy. The choice to use this treatment over FOLFIRINOX is therefore a topic of debate, also because no validated biomarkers to guide FOLFIRINOX treatment are available. In the era of actionable mutations and target agents it would be desirable to identify molecular factors or biomarkers to predict response to therapy in order to maximize the efficacy of treatment and avoid useless toxic effects for non-responding patients. However, until today the milestone of treatment for pancreatic cancer remains chemotherapy combinations, without predictive or monitoring tools existing to optimize therapy. This review analyzes the state-of-the-art treatments, promises and limitations of targeted therapies, ongoing trials and future perspectives, including potential role of microR NAs as predictive biomarkers.

关键词： FOLFIRINOX Personalized therapy New treatments MicroR NA Pancreatic cancer

Mechanical characterization of a 10-MJ HTS SMES magnet wound by quasiisotropic strands and directly stacked tape conductors

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Superconductivity 2023年第1期5卷 69-74页

作者： ZiKun Zhao Yinshun Wang Yubo Gao Zhao Yang ZhuYong Li Wei Pi State Key lab.of New Energy Renewable Power System North China Electric Power UniversityBeijing 102206China Key lab.of hv and EMC Beijing North China Electric Power UniversityBeijing 102206China Energy Singularity Energy Technolo-gy(shanghai)Co. LtdShangHai 200000China

A 10‐MJ‐class superconducting magnetic energy storage(SMES)magnet is designed and optimized in this study using quasi‐isotropic strands and stacked‐tape *** order to ensure the stable operation of SMES systems,it is necessary to evaluate the mechanical properties risk caused by the Lorentz ***,in this study,the magnetic stress caused by the Lorentz force is analyzed using the finite element *** results show that the tapes near the inner diameter of the magnet are subjected to a higher stress and require considerable *** the maximum stress is increased by two times due to the presence of the screening current,it is within the safety *** screening current does not vanish after the discharge *** discharge,the coil is still subjected to a stress on the other of a few MPa.

关键词： Lorentz force Quasi‐isotropic strand Superconducting magnetic energy storage Screening current Weibull distribution

Targeted therapies in cancer:where are we going?

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Cancer Drug Resistance 2018年第2期1卷 82-86页

作者： Elisa Giovannetti Jose A.Rodriguez Department Medical Oncology Lab Medical OncologyVU University Medical CenterCancer Center AmsterdamAmsterdam 1081HVThe Netherlands. Cancer Pharmacology lab AIRC Start Up UnitUniversity of PisaPisa 56100Italy. Department of Genetics Physical Anthropology and Animal PhysiologyUniversity of the Basque CountryBarrio Sarriena s/nLeioa 48940Spain.

SPECIAL ISSUE INTRODUCTION Targeted therapies in cancer aim to specifically block the activity of crucial proteins or signaling pathways necessary for the growth and/or survival of tumor cells.A major breakthrough in targeted cancer therapy was the introduction nearly two decades ago of imatinib,an inhibitor of the BCR-ABL tyrosine kinase for the treatment of chronic myeloid *** the last years,significant advances in our understanding of tumor biology have facilitated the development of many drugs targeting not only kinases,but also other protein families and cellular *** of these agents are currently employed or being implemented for the treatment of different hematologic and solid malignancies,such as lung *** special issue on“Targeted cancer therapy”will include reviews and commentaries updating the clinical use of targeted agents in the treatment of different tumor types,and the mechanisms that underlie the action of drugs directed to different types of *** special issue will also include research articles presenting novel outstanding data on all aspects of targeted cancer *** submissions will undergo rigorous peer review and will be published free of charge upon acceptance.

关键词： drugs Targeted lung

Resistance to epidermal growth factor receptor inhibition in non-small cell lung cancer

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Cancer Drug Resistance 2018年第4期1卷 230-249页

作者： Nele Van Der Steen Elisa Giovannetti Daniela Carbone Alessandro Leonetti Christian D.Rolfo Godefridus J.Peters Department of Medical Oncology VU University Medical CenterAmsterdam 1081 HVthe Netherlands Department of Pathology Antwerp University HospitalAntwerp 2650Belgium Center for Oncological Research University of AntwerpAntwerp 2610Belgium Cancer Pharmacology lab AIRC Start-Up UnitUniversity of PisaPisa 56124Italy Medical Oncology Unit University Hospital of ParmaParma 43126Italy University of Maryland Greenebaum Comprehensive Cancer Center Baltimore21220 MDUSA

Aberrant activation of the epidermal growth factor receptor(EGFR)is a driving force for cancer growth in a subgroup of non-small cell lung cancer *** patients can be identified by the presence of activating EGFR *** three generations of EGFR-tyrosine kinase inhibitors(TKIs)have been approved by the Food and Drug Administration and European Medicine *** paper reviews the structure of EGFR and the downstream signaling pathways of EGFR and describes the mechanisms of intrinsic and acquired resistance against *** mechanisms include secondary or tertiary mutations in EGFR,the activation of bypassing signaling pathways or a histological transformation to small cell lung ***,drug efflux transporters will affect the cellular accumulation of EGFR-TKIs and penetration of the first generation of EGFR-TKI into the *** sequestration of some EGFR-TKIs may also prevent the drugs to reach their *** conclusion,resistance to EGFR-TKIs is multifactorial,including primary and acquired mutations in the EGFR gene,activation of bypassing pathways and limited uptake of drugs in the cells or target *** pharmacological studies are needed in order to develop new specific compounds targeted to overcome new resistance mechanisms in order to enable a personalized treatment approach.

关键词： Epidermal growth factor receptor non-small cell lung cancer resistance EGFR-tyrosine kinase inhibitors erlotinib gefitinib afatinib osimertinib rociletinib

Bio-renewable polymers based on lignin-derived phenol monomers:Synthesis,applications,and perspectives

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SusMat 2022年第5期2卷 535-568页

作者： Weijun Yang Hui Ding Debora Puglia Jose M Kenny Tianxi Liu Jiaqi Guo Qingwen Wang Rongxian Ou Pengwu Xu Piming Ma Pieter Jan Lemstra The Key laboratory of Synthetic and Biological Colloids Ministry of EducationJiangnan UniversityWuxiChina Civil and Environmental Engineering Department Materials Engineering CenterPerugia UniversityUdR INSTMTerniItaly Jiangsu Co-Innovation Center for Efficient Processing and Utilization of Forest Resources and Joint International Research lab of Lignocellulosic Functional Materials Nanjing Forestry UniversityNanjingChina Key laboratory for Bio-based Materials and Energy of Ministry of Education College of Materials and EnergySouth China Agricultural UniversityGuangzhouChina PlemPolco B.V. De Zicht 115502 HVVeldhovenThe Netherlands

In recent decades,the continuous depletion of fossil fuels and the increasingly serious environmental issue have aroused wide attention on the development of biopolymers based on renewable *** is the second most abundant organic bio-based macromolecule second to cellulose,and it can be widely found in ***,various phenol derivatives can be obtained by their depolymerization *** development of bio-renewable polymeric materials originating from lignin-derivative phenol monomers,such as vanillin,syringaldehyde,eugenol,vanillyl alcohol,vanillic acid,and ferulic acid,will not only valorize the bio-sourced materials but also effectively reduce petroleum resource consumption and mitigate the environmental ***,an updated overview of the synthesis processes of these bio-based polymers developed in the past decade,which includes both thermosets and thermoplastics such as epoxy,phenolic,polyimine,polybenzoxazine,polyurethane,and polyesters,are *** addition,the applications of these bio-based polymers and their composites in flame-retarded materials,degradable and reprocessable materials,dielectric materials,optoelectronic materials,as well as smart responsive materials are also intensively *** line with the gradual development of synthesis technologies,we believe that derivatives of lignin will turn into one of the most promising materials to be considered for the preparation of high-performance and functional bio-based polymer materials.

关键词： applications lignin phenol derivatives renewable polymers synthesis

Effects of Heat Treatments on Microstructures and Precipitation Behaviour of Mg_(94)Y_4Zn_2 Extruded Alloy

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Journal of Materials Science & Technology 2014年第2期30卷 128-133页

作者： Huan Liu Feng Xue Jing Bai Jian Zhou Yangshan Sun School of Materials Science and Engineering Jiangsu Key Lab for Advanced Metallic MaterialsSoutheast University

Microstructures and precipitation behaviours of Mg94Y4Zn2 （at. %） extruded alloy during solution treatment and ageing processes were investigated. Three major phases were observed in the as-cast Ug94Zn2Y4 alloy：α-Mg, block shaped 1 8R long period stacking ordered （LPSO） phase and Mg24Y5 cuboid particles. After homogenization and extrusion, the block shaped LPSO phase changed into plate-like shape aligned along the direction of extrusion. During solution treatment, a small fraction of LPSO phase was transformed from 18R structure to 14H type. The nano-scale β＇ phase with its close-packed planes being perpendicular to the direction of both α-Mg and LPSO structure was precipitated at ageing stage. The coexistence of β＇ and LPSO phase contributes to the strengthening of the alloy, with microhardness for the matrix and LPSO structures reaching 145.8 and 155,0 hv, respectively.

关键词： Heat treatment Microstructure Precipitation behaviour Mg94Y4Zn2 alloy Long period stacking ordered structure

Effects of Thermomechanical Treatment on the Mechanical Properties and Microstructures of 6013 Alloy

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Journal of Wuhan University of Technology(Materials Science) 2009年第2期24卷 198-201页

作者：何立子 Key lab of Electromagnetic Processing of Materials Ministry of Education Northeastern University

The mechanical properties and microstructures of 6013 alloy after different thermomechanical treatments were investigated. The detailed dislocation configurations after deformation and morphologies of age hardening precipitates were examined through transmission electron microscopy （TEM）. The experimental results show that the thermomechanical treatment can significantly enhance the strength of 6013 alloy, and has a similar influence trend on single and two-step aging behaviors. With the increasing deformation ratio, the peak-hardness （hvmax） increases, the time to hv shortens, and the density of tangled dislocation network increases. The aging precipitates become larger and inhomogeneous by applying thernomechanical treatment.

关键词： 6013 alloy thermomechanical treatment aging dislocation

Characterization of γ′ precipitates in a nickel base superalloy quenching from aging temperature at different rates

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Rare Metals 2010年第2期29卷 204-208页

作者： LI Hongyu, SONG Xiping, WANG Yanli, and CHEN Guoliang State Key lab for Advanced Metals and Materials, University of Science and Technology Beijing, Beijing 100083, China State Key lab for Advanced Metals and Materials University of Science and Technology Beijing Beijing China

The characteristics of γ′ precipitates in a superalloy quenched from 1050°C at different rates were investigated using field emission scanning electron microscope（FESEM）.When quenched from 1050°C, the size of primary aging γ′ precipitates has a small increase in the specimens that experienced iced-brine-quenching, oil-quenching, and air-cooling-quenching conditions and a drastic increase in the specimen that experienced a furnace-cooling-quenching *** cooling γ′ precipitates have unimodal distributions after quenching at the air-cooling rate and bimodal distributions after quenching at the furnace-cooling rate, but there are not these distributions in the specimens that experienced iced-brine-quenching and oil-quenching *** aging at 760°C, the size of primary aging γ′ precipitates appears unaffected in the specimens that experienced iced-brine-quenching, oil-quenching, and air-cooling-quenching ***, it has a drastic increase in the specimen that experienced a furnace-cooling-quenching condition, and it is interesting that the bigger cooling γ′ precipitates have a coalescence and octodendritic *** microhardness study indicates that the hardness has no variation in the specimens that experienced iced-brine-quenching, oil-quenching, and air-cooling-quenching conditions and has a drastic decrease in the specimens that experienced a furnace-cooling-quenching condition and obtains the minimum microhardness value 390.8 hv.

关键词： superalloys precipitates quenching rate microhardness

Microstructure Characteristics of SiC Particle-Reinforced Aluminum Matrix Composites Coatings by Cold Spraying

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稀有金属材料与工程 2012年第S1期41卷 460-463页

作者： Wang Hongtao Ji Gangchang Chen Xiao Bai Xiaobo Chen Qinyu Jiujiang Univ Jiujiang Key Lab Green Remfg Jiujiang 332005 Peoples R China

A dense Al/SiCp composite coating with high volume fraction(60%)of nano SiCp reinforcement was fabricated by cold spraying of ball-milled Al-60SiCp composite *** morphologies evolution of the Al-60SiCp composite powder during ball milling and the microstructure and microhardness of the cold-sprayed Al-60SiCp composite coating were *** results show that Al particles undergone fracture deformation and nano SiC particles are uniformly distributed in soft Al matrix after ball milling.A dense Al-60SiCp composite coating can be fabricated by cold spraying of ball milled composite *** SiC particles in the cold-sprayed Al-60SiCp composites coating exhibit a reasonably uniform *** hv0.5 microhardness of the Al-60SiCp composite coating is reached up to(5.30±0.53)GPa due to the enhancement of SiC particles,compared to(0.34±0.03)GPa for the pure Al bulk.

关键词： cold spraying ball milling aluminum matrix composites microstructure