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Clinical and pathological characterization of epstein-barr virus-associated gastric carcinomas in portugal

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World Journal of Gastroenterology 2017年第40期23卷 7292-7302页

作者： Joana Ribeiro Andreia Oliveira Mariana Malta Claudia Oliveira Fernanda Silva Ana Galaghar Luís pedro Afonso Maria Cassiano Neves Rui Medeiros pedro pimentel-nunes Hugo Sousa Molecular Oncology and Viral Pathology Group Portuguese Oncology Institute of Porto Faculty of Medicine of Porto University Department of Pathology Portuguese Oncology Institute of Porto Medical Oncology Department Portuguese Oncology Institute of Porto Instituto CUF de Oncologia Virology Service Portuguese Oncology Institute of Porto Research Department-Portuguese League Against Cancer(Liga Portuguesa Contra o Cancro-Núcleo Regional do Norte) Gastroenterology Service Portuguese Oncology Institute of Porto CINTESIS-Center for Health Technology and Services Research(Centro de Investigacao Médica Faculdade de Medicina da Universidade do Porto)

AIM To determine the prevalence of epstein-barr virus(eb V)-associated gastric carcinomas in the North Region of Portugal and to study its clinicopathological characteristics. METHODS We have performed a retrospective study including a total of 179 consecutive patients with gastric cancer(GC) submitted to gastrectomy during 2011 at the Portuguese Oncology Institute of Porto. Clinical and pathological data was collected from individual clinical records and inserted on a database with unique codification. Tumour tissues were collected from the institutional tumour bank. eb V was detected by in situ hybridization for the detection of eb V-encoded small RNAs(ebe Rs) and eb V latent proteins(LMP1 and LMP2 A) were detected by *** The analysis showed that eb V-associated gastric carcinomas(eb Va GC) represents 8.4%(15/179) of all GC cases, with a significant differential distribution among histological types(P < 0.001): 100%(3/3) of medullary carcinomas, 100%(1/1) of adenosquamous carcinoma, 8.7%(8/92) of tubular adenocarcinomas, 8.0%(2/25) of mixed carcinomas and 2%(1/51) in poorly cohesive carcinomas. The analysis revealed a higher predominance of eb Va GC in the upper third and middle(cardia, fundus and body) of the stomach(P = 0.041), a significant lower number of regional lymph nodes invasion(P = 0.025) and a tendency for better prognosis(P = 0.222). eb V latent protein expression revealed that all eb Va GC cases were LMP1-negative, nevertheless 6 cases(40%) expressed LPM2 A, which reveals that these cases show a distinct eb V-Latency profile(latency II-like).CONCLUSION eb Va GC represents 8.4% of all GC in the North Region of Portugal. The eb V-infected patients have specific clinic-pathological features that should be further explored to develop new strategies of management and treatment.

关键词： Gastric cancer Epstein-barr virus Prevalencel Epstein-barr virus-associated gastric carcinomas

Helicobacter pylori-induced inflammation masks the underlying presence of low-grade dysplasia on gastric lesions

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World Journal of Gastroenterology 2020年第26期26卷 3834-3850页

作者： Alba Panarese Giovanni Galatola Raffaele Armentano pedro pimentel-nunes Enzo Ierardi Maria Lucia Caruso Francesco Pesce Marco Vincenzo Lenti Valeria Palmitessa Sergio Coletta Endrit Shahini Department of Gastroenterology and Digestive Endoscopy National Institute of Gastroenterology"S De Bellis"Research HospitalCastellana Grotte 70013Italy Department of Clinical Pathology National Institute of Gastroenterology"S De Bellis"Research HospitalCastellana Grotte 70013Italy Center for Research in Health Technologies and Information Systems Faculty of MedicinePorto 4200072Portugal Surgery and Physiology Department Faculty of Medicine of the University of PortoPorto 4200072Portugal Department of Emergency and Organ Transplantation University of BariBari 70124Italy Nephrology Section Department of Emergency and Organ TransplantationUniversity of BariBari 70124Italy First Department of Internal Medicine San Matteo Hospital FoundationUniversity of PaviaPavia 27100Italy Laboratory of Microbiology and Virology National Institute of Gastroenterology"S De Bellis"Research HospitalCastellana Grotte 70013Italy Gastroenterology Unit Institute for Cancer Research and TreatmentTurin 10121Italy

BACKGROUND Helicobacter pylori(***)infection has been associated with a long-term risk of precancerous gastric conditions(PGC)even after *** *** To investigate the efficacy of High-Resolution White-Light Endoscopy with Narrow-Band Imaging in detecting PGC,before/after *** *** We studied 85 consecutive patients with ***-related gastritis with/without PGC before and 6 mo after proven *** ***-Takemoto modified and endoscopic grading of gastric intestinal metaplasia classifications,were applied to assess the endoscopic extension of atrophy and intestinal *** histological result was considered to be the gold *** Sydney System,the Operative-Link on Gastritis-Assessment,and the Operative-Link on Gastric-Intestinal Metaplasia were used for defining histological gastritis,atrophy and intestinal metaplasia,whereas dysplasia was graded according to World Health Organization *** anti-parietal cell antibody and anti-intrinsic factor were measured when autoimmune atrophic gastritis was *** After *** eradication histological signs of mononuclear/polymorphonuclear cell infiltration and Mucosal Associated Lymphoid Tissue-hyperplasia,disappeared or decreased in 100%and 96.5%of patients respectively,whereas the Operative-Link on Gastritis-Assessment and Operative-Link on Gastric-Intestinal Metaplasia stages did not ***-Grade Dysplasia prevalence was similar on random biopsies before and after *** eradication(17.6%vs 10.6%,P=0.19),but increased in patients with visible lesions(0%vs 22.4%,P<0.0001).At a multivariate analysis,the probability for detecting dysplasia after resolution of ***-related active inflammation was higher in patients with regression or reduction of Mucosal Associated Lymphoid Tissue hyperplasia,greater alcohol consumption,and anti-parietal cell antibody and/or anti-intrinsic factor positivity[odds ratio(OR)=3.88,95%confidence i

关键词： Autoimmune gastritis Dysplasia Diagnosis Malignancy Gastric cancer Symptoms Signs

Toll-Like Receptors as Biomarkers of Gastric Carcinogenesis:Implications for Diagnosis,Prognosis and Treatment

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Journal of Cancer Therapy 2013年第5期4卷 1037-1047页

作者： pedro pimentel-nunes Joao Bruno Soares Mário Dinis-Ribeiro Department of Physiology Cardiovascular Research&Development UnitFaculty of MedicineUniversity of PortoPortoPortugal Gastroenterology Department Portuguese Oncology InstitutePortoPortugal Gastroenterology Department Hospital de BragaBragaPortugal CIDES/CINTESIS Faculty of MedicineUniversity of PortoPortoPortugal

Toll-like receptors (TLR) are essential for Helicobacter pylori (Hp) recognition and subsequent innate and adaptive immunity responses. TLR2 appears to be the receptor responsible for most of the immunologic reaction against Hp infection. However, TLR4, TLR9 and eventually TLR5 may also have a synergic effect with TLR2 against Hp. It has been shown that gastric Hp infection increases TLR expression in the gastric mucosa. Moreover, recent studies have shown that human gastric carcinogenesis is associated not only with increased expression of TLR but also with decreased expression of their inhibitors such as Toll-Interacting Protein (TOLLIP) and peroxisome proliferator-activated receptor (PPAR)-g. Indeed, gastric dysplasia and adenocarcinoma are associated with high expression levels of TLR and low levels of TOLLIP and PPAR-g, suggesting increased activation of these receptors throughout human gastric carcinogenesis. In this article we discuss how these novels findings could be used not only for the diagnosis and prognosis of gastric lesions associated with Hp infection but also for their treatment. Specifically, we discuss the potential use of TLR agonists in addition to antibiotics to improve eradication rates of Hp and of TLR antagonists to slow the progression of gastric preneoplastic lesions. We also discuss the potential value of TLR signalling blockers and quantification of tumoral TLR expression, respectively, in the treatment and prognosis of gastric cancer. In conclusion, TLRs can be an important link between Hp and the sequence of gastric carcinogenesis and they can be used as biomarkers of gastric carcinogenesis. In this article, future lines of investigation related with these novel scientific findings are proposed and discussed.

关键词： Toll-Like Receptors Gastric Cancer TOLLIP Carcinogenesis Helicobacter pylori

Helicobacter pylori and microRNAs:Relation with innate immunity and progression of preneoplastic conditions

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World Journal of Clinical Oncology 2015年第5期6卷 111-132页

作者： Diogo Libanio Mário Dinis-Ribeiro pedro pimentel-nunes Gastroenterology Department Portuguese Oncology Institute Center for Health Technology and Services Resarch Faculty of Medicine University of Porto Department of Health Information and Decision Sciences Faculty of Medicine University of Porto Department of Physiology and Cardio- thoracic Surgery Cardiovascular Research and Development UnitFaculty of Medicine University of Porto

The accepted paradigm for intestinal-type gastric cancer pathogenesis is a multistep progression from chronic gastritis induced by Helicobacter pylori(H. pylori) to gastric atrophy, intestinal metaplasia, dysplasia and ultimately gastric cancer. The genetic and molecular mechanisms underlying disease progression are still not completely understood as only a fraction of colonized individuals ever develop neoplasia suggesting that bacterial, host and environmental factors are involved. Micro RNAs are noncoding RNAs that may influence H. pylori-related pathology through the regulation of the transcription and expression of various genes, playing an important role in inflammation, cell proliferation, apoptosis and differentiation. Indeed, H. pylori have been shown to modify micro RNA expression in the gastric mucosa and micro RNAs are involved in the immune host response to the bacteria and in the regulation of the inflammatory response. Micro RNAs have a key role in the regulation of inflammatory pathways and H. pylori may influence inflammation-mediated gastric carcinogenesis possibly through DNA methylation and epigenetic silencing of tumor suppressor micro RNAs. Furthermore, micro RNAs influenced by H. pylori also have been found to be involved in cell cycle regulation, apoptosis and epithelial-mesenchymal transition. Altogether, micro RNAs seem to have an important role in the progression from gastritis to preneoplastic conditions and neoplastic lesions and since each micro RNA can control the expression of hundreds to thousands of genes, knowledge of micro RNAs target genes and their functions are of paramount importance. In this article we present a comprehensive review about the role of micro RNAs in H. pylori gastric carcinogenesis, identifying the micro RNAs downregulated and upregulated in the infection and clarifying their biological role in the link between immune host response, inflammation, DNA methylation and gastric carcinogenesis.

关键词： Helicobacter pylori MicroRNA Gastric cancer Inflammation DNA methylation Preneoplastic conditions Stomach neoplasms Immune response

Innate immunity and hepatocarcinoma:Can toll-likereceptors open the door to oncogenesis?

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World Journal of Hepatology 2016年第3期8卷 162-182页

作者： Jorge AndréGomes Lopes Marta Borges-Canha pedro pimentel-nunes Department of Physiology and Cardiothoracic Surgery Cardiovascular Research and Development UnitFaculty of MedicineUniversity of Porto4200-319 PortoPortugal Gastroenterology Department Portuguese Oncology Institute4200-072 PortoPortugal CINTESIS/Department of Biostatistics and Medical Informatics Faculty of MedicineUniversity of Porto4200-319 PortoPortugal

Hepatocarcinoma(HCC) is a highly prevalent cancer worldwide and its inflammatory background was established long *** studies have shown that innate immunity is closely related to the HCC *** effective innate immunity response relies on the tolllike receptors(TLR) found in several different liver cells which,through different ligands and many signaling pathways can elicit,not only a pro-inflammatory but also an oncogenic or anti-oncogenic *** aim was to study the role of TLRs in the liver oncogenesis and as a consequence their value as potential therapeutic *** performed a systematic review of PubMed searching for original articles studying the relationship between HCC and TLRs until March ***2 appears to be a fundamental stress-sensor as its absence reveals an augmented tendency to accumulate DNAdamages and to cell ***,pathways are still not fully understood as TLR2 up-regulation was also associated to enhanced ***3 has a wellknown protective role influencing crucial processes like angiogenesis,cell growth or ***4 works as an interesting epithelial-mesenchymal transition's inducer and a promoter of cell survival probably inducing HCC carcinogenesis even though an anti-cancer role has already been ***9's influence on carcinogenesis is also controversial and despite a potential anticancer capacity,a pro-tumorigenic role is more *** polymorphisms in some TLRs have been found and its influence on the risk of HCC has been *** therapeutic targets,TLRs are already in use and have a great *** conclusion,TLRs have been shown to be an interesting influence on the HCCs microenvironment,with TLR3 clearly determining an antitumour ***4 and TLR9 are considered to have a positive relationship with tumour development even though,in each of them anti-tumorigenic signals have been ***2 presents a more ambiguous role,possibly depending on the stag

关键词： Hepatocarcinoma Carcinogenesis Toll-likereceptor Innate immunity Chronic inflammation

Employing electrochemically derived pH gradients for Lab-on-PCB protein preconcentration devices

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Microsystems & Nanoengineering 2024年第1期10卷 79-87页

作者： Grace Maxted pedro Estrela Despina Moschou Department of Electronic and Electrical Engineering University of BathBath BA27AYUK Centre for Bioengineering and Biomedical Technologies(CBio) University of BathBath BA27AYUK

Protein preconcentration is an essential sample preparation step for analysis in which the targeted proteins exist in low concentrations,such as bodily fluids,water,or ***,very few practical implementations of miniaturized protein preconcentration devices have been demonstrated in practice,and even fewer have been integrated with other microanalytical *** approaches rely heavily on additional chemicals and reagents and introduce complexity to the overall *** this paper,we propose a novel miniaturized isoelectric focusing-based protein preconcentration screening device based on electrochemically derived pH gradients rather than existing chemical reagent *** this way,we reduce the need for additional chemical reagents to zero while enabling device incorporation in a seamlessly integrated full protein analysis microsystem via Lab-on-PCB *** apply our previously presented Lab-on-PCB approach to quantitatively control the pH of a solution in the vicinity of planar electrodes using electrochemical acid generation through redox-active self-assembled *** presented device comprises a printed circuit board with an array of gold electrodes that were functionalized with 4-aminothiophenol;this formed a self-assembled monolayer that was electropolymerized to improve its electrochemical *** preconcentration was performed in two *** first was open and needed the use of a holder to suspend a well of fluid above the electrodes;the second used microfluidic channels to enclose small volumes of *** here are the resulting data for protein preconcentration in both these forms,with a quantitative concentration factor shown for the open form and qualitative proof shown for the microfluidic.

关键词： electrochemical proof qualitative

Conformational dynamics as an intrinsic determinant of prion protein misfolding and neurotoxicity

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Neural Regeneration Research 2024年第10期19卷 2095-2096页

作者： Alessandro Cembran pedro Fernandez-Funez Department of Chemistry and Biochemistry University of Minnesota DuluthDuluthMNUSA Department of Biomedical Sciences University of Minnesota Medical SchoolDuluth CampusDuluthMNUSA

The prion protein(PrP) is the key molecular and pathological mediator of prion diseases,a heterogeneous group of brain disorders with fatal *** diseases are rare but deserve special attention because of their unique f... 详细信息

关键词： folding intrinsic dynamics

Effect of the Coulomb and dielectric forces on the onset of Rayleigh-Bénard convection

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Acta Mechanica Sinica 2024年第6期40卷 64-77页

作者： Zhonglin Du pedro A.Vázquez Jian Wu School of Energy Science and Engineering Harbin Institute of TechnologyHarbin150001China Heilongjiang Key Laboratory of Micro-and Nano-scale Fluid Flow and Heat Transfer Harbin150001China Departamento de Física Aplicada III ETSIIUniversidad de SevillaSevilla41092Spain

In this paper,the effect of Coulomb and dielectric forces on the onset of Rayleigh-Bénard convection(RBC)in a dielectric liquid layer contained between two parallel electrode plates has been numerically *** different operating conditions have been considered in electrohydrodynamic(EHD)conduction:ohmic and saturation,and variations in the physical properties of the dielectric fluid with *** electric equations and the state equations based on the Boussinesq approximation are integrated in the framework of OpenFOAM buoyantBoussinesqPimpleFoam *** results show that in the ohmic regime,the combined effect of Coulomb and dielectric forces promotes the onset of RBC flow,while in the saturation state,the inhibition of RBC flow by Coulomb force is more *** value of the critical Rayleigh number Ra decreases with increasing electric Reynolds number ReE in the ohmic regime,whereas in the saturation state,the critical Ra increases with increasing *** the saturation regime,the flow field always has a steady flow in the range of parameters ***,the onset of the RBC flow promoted by the dielectric force is more pronounced in the ohmic *** to the presence of the dielectric force,the flow field exhibits periodic oscillatory flow at low electric Reynolds numbers for the range of parameters considered.

关键词： EHD conduction Dielectric force Rayleigh-Bénard convection OpenFOAM

Inversion of walkaway VSP data in the presence of lateral velocity heterogeneity

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Energy Geoscience 2024年第2期5卷 304-313页

作者： Vladimir Grechka Ilya Tsvankin pedro Contreras CWP Department of GeophysicsColorado School of MinesGoldenCO80401USA PDVSA-INTEVEP Apartado 76343Caracas1070AVenezuela Borehole Seismic LLC USA Department of Physics ULAVenezuela

Multi-azimuth walkaway vertical seismic profiling is an established technique for the estimation of in situ slowness surfaces and inferring anisotropy ***,this technique requires the assumption of lateral homogeneity,which makes the horizontal slowness components at depths of downhole receivers equal to those measured at the *** violations of this assumption,such as lateral heterogeneity or nonzero dip of intermediate interfaces,lead to distortions in reconstructed slowness surfaces and,consequently,to errors in estimated anisotropic *** this work,we relax the assumption of lateral homogeneity and discuss how to correct vertical seismic profile data for weak lateral *** describe a procedure of downward continuation of recorded traveltimes that accounts for the presence of both vertical inhomogeneity and weak lateral heterogeneity,which produces correct slowness surfaces at depths of downhole receivers,noticing that sufficiently dense receiver coverage along a borehole is required to separate influences of vertical and lateral heterogeneity on measured traveltimes and obtain accurate estimates of the slowness *** the slowness surfaces are found and a desired type of anisotropic model to be inverted is selected,the corresponding anisotropic parameters,providing the best fit to the estimated slownesses,can be *** invert the slowness surfaces of P-waves for parameters of the simplest anisotropic model describing dipping fractures(transversely isotropic medium with a tilted symmetry axis).Five parameters of this model,namely,the P-wave velocity V0 in the direction of the symmetry axis,Thomsen's anisotropic coefficients e and d,the tilt n,and the azimuth b of the symmetry axis,can be estimated in a stable manner when maximum source offset is greater than half of receiver depth.

关键词： Walkaway vertical seismic profile Lateral velocity heterogeneity Anisotropic parameter estimation Vertical inhomogeneity