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Glycoproteogenomics: Setting the Course for Next-generation Cancer Neoantigen Discovery for Cancer Vaccines

Genomics, Proteomics & Bioinformatics 2021年第1期19卷 25-43页

作者： José Alexandre Ferreira Marta Relvas-santos Andreia Peixoto AndréM.N.Silva lúcio lara santos Experimental Pathology and Therapeutics Group Portuguese Institute of OncologyPorto 4200-072Portugal Institute of Biomedical Sciences Abel Salazar University of PortoPorto 4050-313Portugal Porto Comprehensive Cancer Center(P.ccc) Porto 4200-072Portugal REQUIMTE-lAQV Department of Chemistry and BiochemistryFaculty of Sciences of the University of PortoPorto 4169-007Portugal

Molecular-assisted precision oncology gained tremendous ground with high-throughput next-generation sequencing(NGS),supported by robust *** quest for genomicsbased cancer medicine set the foundations for improved patient stratification,while unveiling a wide array of neoantigens for *** pre-clinical and clinical studies have successfully used tumor-specific peptides in vaccines with minimal off-target ***,the low mutational burden presented by many lesions challenges the generalization of these solutions,requiring the diversification of neoantigen *** utilizing customized databases for protein annotation by mass spectrometry(MS)is a powerful tool toward this *** the concept toward exploring proteoforms originated from post-translational modifications(PTMs)will be decisive to improve molecular subtyping and provide potentially targetable functional nodes with increased cancer *** through the path of systems biology,we highlight that alterations in protein glycosylation at the cell surface not only have functional impact on cancer progression and dissemination but also originate unique molecular fingerprints for targeted ***,we discuss the outstanding challenges required to accommodate glycoproteomics in oncoproteogenomics *** envisage that such rationale may flag a rather neglected research field,generating novel paradigms for precision oncology and immunotherapy.

关键词： Glycoproteogenomics Oncoproteogenomics Cancer neoantigens Glycosylation Precision oncology

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Personalizing therapies for gastric cancer: Molecular mechanisms and novel targeted therapies

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World Journal of Gastroenterology 2013年第38期19卷 6383-6397页

作者： Michael luis Ana Tavares liliana S Carvalho lúcio lara-santos António Araújo Ramon Andrade de Mello Gastrointestinal Unit Service of Medical OncologyPortuguese Oncology Institute4200-072 PortoPortugal Gastrointestinal Unit Experimental Pathology and Therapeutics GroupResearch Center-Portuguese Oncology Institute4200-072 PortoPortugal Department of Pharmacology and Therapeutics Faculty of MedicineUniversity of Porto4200-319 PortoPortugal Institute of Cellular and Molecular Biology 4150-180 PortoPortugal Gastrointestinal Unit Section of Surgical OncologyPortuguese Oncology Institute4200-072 PortoPortugal Department of Medicine Faculty of MedicineUniversity of Porto4200-319 PortoPortugal

Globally,gastric cancer is the 4thmost frequently diagnosed cancer and the 2ndleading cause of death from cancer,with an estimated 990000 new cases and738000 deaths registered in *** the advanced setting,standard chemotherapies protocols acquired an important role since last decades in prolong ***,recent advances in molecular therapies provided a new interesting weapon to treat advanced gastric cancer through anti-human epidermal growth factor receptor 2(HER2)***,an anti-HER2 monoclonal antibody,was the first target drug in the metastatic setting that showed benefit in overall survival when in association with platinum-5-fluorouracil based ***,HER2 overexpression analysis acquired a main role in predict response for trastuzumab in this ***,we conducted a review that will discuss the main points concerning trastuzumab and HER2 in gastric cancer,providing a comprehensive overview of molecular mechanisms and novel trials involved.

关键词： Gastric cancer Human epidermal growth factor receptor 2 Biomarkers Target therapies Trastuzumab lapatinib Pertuzumab Trastuzumab-DM1 Afatinib

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Contribution of mechanical forces to structural synaptic plasticity:insights from 3D cellular motility mechanisms

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Neural Regeneration Research 2025年第7期20卷 1995-1996页

作者： Rita O.Teodoro Mafalda Ribeiro Ramos lara Carvalho iNOVA4Health NOVA Medical School|Faculdade de Ciências MédicasNMS|FCMUniversidade Nova de LisboaLisboaPortugal

Cells,tissues,and organs are constantly subjected to the action of mechanical forces from the extracellular environment-and the nervous system is no ***-intrinsic properties such as membrane lipid composition,abundance of mechanosensors,and cytoskeletal dynamics make cells more or less likely to sense these *** and extrinsic cues are integrated by cells and this combined information determines the rate and dynamics of membrane protrusion growth or retraction(Yamada and Sixt,2019).Cell protrusions are extensions of the plasma membrane that play crucial roles in diverse contexts such as cell migration and neuronal synapse *** the nervous system,neurons are highly dynamic cells that can change the size and number of their pre-and postsynaptic elements(called synaptic boutons and dendritic spines,respectively),in response to changes in the levels of synaptic activity through a process called *** plasticity is a hallmark of the nervous system and is present throughout our lives,being required for functions like memory formation or the learning of new motor skills(Minegishi et al.,2023;Pillai and Franze,2024).

关键词： plasticity structural mechanisms

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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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Use of improved cold-finger technique to assess effects of basicity on heat transfer through solidified mold flux

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Journal of Iron and Steel Research International 2019年第4期26卷 393-402页

作者： Karina lara santos Assis Petrus Christiaan Pistorius Department of Materials Science and Engineering Center for Iron and Steelmaking ResearchCarnegie Mellon UniversityPittsburgh 15213PAUSA

Cold-finger measurements were used to estimate the contact resistance and average thermal conductivity of mold flux films solidified on a water-cooled copper *** industrial mold fluxes,with basicities from low to high,were *** steady-state rate of convective heat transfer between the solid film and liquid flux was compared with calculations based on natural convection correlations;the comparison indicates that the surface of the solid film(in contact with molten flux)is approximately at its solidus *** roughness of the mold flux film in contact with copper was larger for films grown from higher-temperature mold flux and for higher-basicity mold *** glassy(low-basicity)film had an estimated thermal conductivity of 1.1 W/(m K).The crystalline or partially crystalline films had higher estimated thermal conductivities of 2.2-3.2 W/(m K).The measured values of thermal resistance were extrapolated to typical mold flux film thicknesses for industrial conditions;the extrapolations confirmed that the high contact resistance of higher-basicity mold fluxes can yield higher thermal resistances than the low-basicity *** morphology of the rough interface of higherbasicity mold flux films that gives the higher contact resistance is consistent with that observed in previous work and appears not to be directly related to crystallization.

关键词： Mold flux Heat transfer Conduction Contact resistance-Cold-finger technique

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The road to sustainable use and waste management of plastics in Portugal

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Frontiers of Environmental Science & Engineering 2022年第1期16卷 91-106页

作者： Joana C.Prata Ana lPatrício Silva Armando CDuarte Teresa Rocha-santos Centre for Environmental and Marine Studies(CESAM)&Department of Chemistry University of Aveiro3810-193 AveiroPortugal Centre for Environmental and Marine Studies(CESAM)&Department of Biology University of Aveiro3810-193 AveiroPortugal

As a European Union(EU)member,Portugal must comply with reductions in plastic *** Portugal,the 330 items/100 m of beach litter,comprising up to 3.9 million pieces and of which 88%is plastic,is higher than the EU median(149 items/100 m)and must be reduced to 20 items/100 m(94%).Integrative measures are needed to reduce littering and improve plastics’use and disposal under the circular *** this 414 kt of plastic packaging waste,163 kt were declared plastic packaging,140 kt subjected to recycling,and 94 kt to energy *** current recycling rate of plastic packaging(34%)should be improved to reach EU recycling averages(42%)and goals and to provide widespread benefits,considering revenues of 167€/*** a net importer of waste,Portugal could benefit from the valorization of imported *** increased recycling,pyrolysis and gasification could provide short-term alternatives for producing value-added substances from plastic waste,such as hydrogen,consistent with the National Plan of Hydrogen and improving ongoing regulations on single-use *** manuscript provides an integrative view of plastics in Portugal,from use to disposal,providing specific recommendations under the circular economy.

关键词： Single-use plastics Plastic packaging Plastic waste Waste management Waste shipment lightweight plastic bags

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Profiles of Entamoeba histolytica—specific imunoglobulins in human sera

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Asian Pacific Journal of Tropical Medicine 2012年第3期5卷 234-238页

作者： Windell l Rivera Herbert J santos Vanissa A Ong lara Jessica G Murao Institute of Biology College of ScienceUniversity of the PhilippinesDilimanQuezon City 1101Philippines Molecular Protozoology laboratory Natural Sciences Research InstituteUniversity of the PhilippinesDilimanQuezon City 1101Philippines

Objective:To determine the profdes of anti-Entamoeba histolytica(***) ***. and IgM in sera of diarrheic and non-diarrheic individuals and partially characterize target ***:Serum samples from thirty diarrheic and thirty non-diarrheic individuals were subjected to IgA,IgG,and IgM profiling through enzyme-linked immunosorbent assay (***),flow cytometry,and ***:ElBA titer results showed that both diarrheic and non-diarrheic individuals possess high levels of ***-specific IgG compared to IgA and *** cytometry data showed that diarrheic serum samples had higher mean reaction percentages against *** cells compared to non-diarrheic *** *** proteins with molecular weights ranging belween 7 kDa and 292 kDa were recognized by diarrheic serum IgG,and 170 kDa and 250 kDa by non-diarrheic serum IgG. Conclusions:Our findings suggest that serum *** IgG,compared with serum *** IgA and IgM responses,was generally high in both diarrheic and nondiarrheic sera,indicating a past exposure to the organism both in symptomatic patients as well as in asymptomatic carriers,*** addition,serum IgG from diarrheic and non-diarrheic patients were able to detect immunogenic *** proteins.

关键词： Entamoeba histolytica IgA IgG IgM ElISA immunoblot flow cytometry

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Non-destructive microstructural analysis by electrical conductivity:Comparison with hardness measurements in different materials

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Journal of Materials Science & Technology 2019年第3期35卷 360-368页

作者： Gon?alo l.Sorger J.P.Oliveira Patrick l.Inácio Norbert Enzinger Pedro Vila? R.M.Miranda Telmo G.santos Department of Engineering Design and Production School of Engineering Aalto University Department of Materials Science and Engineering The Ohio State University UNIDEMI Departamento de Engenharia Mecanica e Industrial Faculdade de Ciências e Tecnologia Universidade Nova de Lisboa IMAT-Institute of Materials Science Joining and FormingTU Graz

The use of non-destructive evaluation(NDE) techniques for assessing microstructural changes in processed materials is of particular importance as it can be used to assess, qualitatively, the integrity of any material/structure. Among the several NDE techniques available, electrical conductivity measurements using eddy currents attract great attention owing to its simplicity and reliability. In this work, the electrical conductivity profiles of friction stir processed Ti6Al4 V, Cu, Pb, S355 steel and gas tungsten arc welded AISI 304 stainless steel were determined through eddy currents and four-point probe. In parallel, hardness measurements were also performed. The profiles matched well with the optical macrographs of the materials: while entering in the processed region a variation in both profiles was always observed. One particular advantage of electrical conductivity profiles over hardness was evident: it provides a better resolution of the microstructural alterations in the processed materials. Moreover, when thermomechanical processing induces microstructural changes that modify the magnetic properties of a material,eddy currents testing can be used to qualitatively determine the phase fraction in a given region of the material. A qualitative relation between electrical conductivity measurements and hardness is observed.

关键词： Non-destructive evaluation techniques Electrical conductivity Hardness Friction stir processing Gas tungsten arc welding

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Gain of transcription factor binding sites is associated to changes in the expression signature of human brain and testis and is correlated to genes with higher expression breadth

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Science China(life Sciences) 2019年第4期62卷 526-534页

作者： Vandeclécio lira da Silva André Mauricio Ribeiro dos santos Wilfredo Blanco Sandro José de Souza Bioinformatics Multidisciplinary Environment (BioME) Universidade Federal do Rio Grande do Norte (UFRN) Programa de Pós-Gradua??o em Genética e Biologia Molecular (PPGBM) Universidade Federal do Pará (UFPA) Department of Computer Science Universidade Estadual do Rio Grande do Norte (UERN) Brain Institute Universidade Federal do Rio Grande do Norte (UFRN)

The gain of transcription factor binding sites(TFBS) is believed to represent one of the major causes of biological *** we used strategies based on comparative genomics to identify 21,822 TFBS specific to the human lineage(TFBS-HS),when compared to chimpanzee and gorilla genomes. More than 40%(9,206) of these TFBS-HS are in the vicinity of 1,283 genes.A comparison of the expression pattern of these genes and the corresponding orthologs in chimpanzee and gorilla identified genes differentially expressed in human tissues. These genes show a more divergent expression pattern in the human testis and brain, suggesting a role for positive selection in the fixation of TFBS gains. Genes associated with TFBS-HS were enriched in gene ontology categories related to transcriptional regulation, signaling, differentiation/development and nervous ***, genes associated with TFBS-HS present a higher expression breadth when compared to genes in general. This biased distribution is due to a preferential gain of TFBS in genes with higher expression breadth rather than a shift in the expression pattern after the gain of TFBS.

关键词： TFBS transcript factor human evolution expression breadth

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Resistance of stored bean varieties to Acanthoscelides obtectus （Coleoptera： Bruchidae）

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Insect Science 2008年第4期15卷 317-326页

作者： Edson l.l. Baldin Fernando M. lara Department of Plant Production-Faculty of Agronomic Sciences/Sao Paulo State University Botucatu Sao Paulo State Department of Plant Protection Faculty of Agranan and Veterinary Sciences / Sao Paulo State University Zip Code 14884-900 Jaboticabal Sao Paulo State Brazil

During bean seed storage, yield can be lost due to infestations of Acanthoscelides obtectus Say, the bean weevil. The use of resistant varieties has shown promising results in fighting these insects, reducing infestation levels and eliminating chemical residues from the beans. The expression of resistance to A. obtectus in bean varieties is frequently attributed to the presence of phytohemagglutinins, protease inhibitors and alpha-amylase, and especially to variants of the protein arcelin, which reduce the larval viability of these insects. To evaluate the effect of bean seed storage time on the resistance expression of bean varieties to A. obtectus, tests with seeds of three ages （freshly-harvested, 4-month-old, and 8-monthold） were conducted in the laboratory, using four commercial varieties： Carioca Pitoco, Ipa 6, Porrillo 70, Onix; four improved varieties containing arcelin protein： Arc. 1, Arc.2, Arc. 3, Arc.4; and three wild varieties also containing arcelin protein： ***, Arc.3S, and Arc. 5S. The Arc.5S, ***, and Arc.2 varieties expressed high antibiosis levels against the weevil; Arc.1 and Arc3S expressed the same mechanism, but at lower levels. The occurrence of oviposition non-preference was also observed in Arc.5S and Arc. 1S. The Arc.3 and Arc. 4 varieties expressed low feeding non-preference levels against A. obtectus. The expression of resistance in arcelin-bearing, wild or improved varieties was affected during the storage of seeds, and was high under some parameters but low in others. The results showed that addition of chemical resistance factors such as protein arcelin via genetic breeding may be beneficial in improving the performance of bean crops.

关键词： antibiosis antixenosis bean weevil host plant resistance Phaseolus vulgaris

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