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Phytochemicals and cancer chemoprevention

Journal of Cancer Metastasis and Treatment 2020年第1期6卷 575-610页

作者： Asim Dave Falguni Parande Eun-Jung Park John M.Pezzuto arnold&marie schwartz college of pharmacy and health sciences Long Island UniversityBrooklynNY 11201USA college of pharmacy and health sciences Western New England UniversitySpringfieldMA 01119-2684USA

The unending morbidity and mortality that results from cancer,as well as adverse reactions due to chemotherapy and the enormous economic burden of treatment and hospitalization,advocates for the necessity of chemopreventive *** chemoprevention refers to the use of agents capable of reversing,reducing,or slowing down the pathology of cancer at various ***,a few therapeutic drugs with relatively low toxicity(e.g.,tamoxifen,finasteride),and a sparse number of vaccines(hepatitis B,HPV),are used to prevent specific *** the general population,however,therapeutic options for cancer prevention are not ***,it is generally agreed that diet affects the genesis of cancer,and phytochemicals have the capacity of functioning as cancer chemoprevention *** is supported by epidemiological studies and clearly documented with animal models designed to mimic human ***,some public health strategies,such as recommendations for greater consumption of fruits and vegetables,reflect the merits of cancer ***,we focus on some well-established natural product cancer chemopreventive agents,including resveratrol(grapes),epigallocatechin-3-gallate(green tea),sulforaphane(cruciferous vegetables),anthocyanins(grapes and berries),curcumin(turmeric),silibinin(milk thistle),and lycopene(tomatoes).As aptly demonstrated by genomic analysis and other methods,the mechanistic underpinning is variable and *** addition,responses may be mediated through indirect mechanisms,such as interaction with the ***,ancillary applications of chemopreventive agents are worthy of consideration,such as management of sequelae induced by *** the loss of millions of cancer patients every year,it is obvious that negating malignant metastatic conditions remains of paramount *** meeting this objective,cancer chemoprevention offers great promise.

关键词： Chemoprevention phytochemicals resveratrol curcumin anthocyanins silibinin lycopene epigallocatechin-3-gallate anti-cancer activity

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Pentoxifylline suppressed LPS-induced inflammatory and apoptotic signaling in neuronal cells

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Advances in Bioscience and Biotechnology 2012年第6期3卷 731-739页

作者： Sameer K. Muchhala Kenza E. Benzeroual Division of Pharmaceutical sciences Arnold & Marie Schwartz college of Pharmacy & Health Sciences Long Island University Brooklyn NY 11201 USA

Several studies have reported a relation between increased pro-inflammatory mediators such as TNF-α and apoptosis in neurodegenerative diseases such as Alzheimer’s disease (AD). It is known that lipopoly-saccharide (LPS) treatment induces neuroinflammation and memory deterioration, and it has been reported that LPS induces apoptosis mostly through the production of TNF-α. Pentoxifylline (PTX), is a vascular protective agent and a potent TNF-alpha inhibitor. However, the molecular neuroprotective mechanisms of PTX against LPS-induced neurotoxicity have not been well studied. In this study, we investigated the direct protective effect of PTX against LPS-induced toxicity in Rat pheochromocytoma (PC12) cell line. The results showed that a pretreatment with PTX prior exposure to LPS signifycantly decreased LPS-induced cell death. Mechanisms study showed that PTX has the potential to inhibit pro-inflammatory and pro-apoptotic pathways via the suppression of TNF-α and a caspase-dependent pathway in neuronal PC12 cells. This is the first study to report the anti-inflammatory and anti-apoptotic effects of PTX via inhibition of TNF-α and a caspase-dependent pathway in neuronal PC12 cells. Altogether, these observations indicate that PTX is capable of promoting neuroprotective effects, meanwhile also present some insights into the potential signaling pathways that are involved. Thus, these findings support the potential for PTX to be investigated as a potential agent for the treatment of neurodegenerative diseases such as AD.

关键词： Pentoxifylline Lipopolysaccharide (LPS) Neuronal Cells Apoptosis Inflammatory Cytokines Neurodegeneration Tnf-Alpha Alzheimer’s Disease

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Ionization and transfection activity of n-methyl-substituted carbamoyl-cholesterol derivatives

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Journal of Biophysical Chemistry 2011年第2期2卷 53-62页

作者： Samuel Acheampong Michalakis Savva Division of pharmaceuticals sciences Arnold & Marie Schwartz College of Pharmacy & Health Sciences Long Island University New York United States

Five novel cationic lipids, the polar head group of which was attached to the cholesterol backbone via a tertiary carbamate linker, were synthesized and their physicochemical properties were compared to their transfection efficiencies. Transfection activity of the primary amine analog was highest among the series, while the quaternary ammonium iodide salt was essentially transfection incompetent. Contrary to DC-Chol, methyl and ethyl carbamoyl derivatives of DC-Chol mediated high levels of transfection in the absence of DOPE. Ionization of the cationic assemblies in 40 mM Tris buffer pH 7.2 exactly correlated with the competitive nature of the inductive and steric effects of the methyl groups on the aliphatic nitrogen of the lipids’ polar moiety. Interestingly, the pH interaction zone of all lipid dispersions at 25°C was extended by ± 2 pH units from the pKa, while the pKa of the cationic lipids determined in mixed vesicles composed of 90 % DOPC and cholesterol was approximately 1.3 to 1.5 times higher than that of pure cationic assemblies. The interaction of cationic lipids with plasmid DNA was correlated with pKa, but not the transfection activity.

关键词： Cationic Lipids DC-Chol Transfection Pka Plasmid DNA Monolayer Surface Pressure.

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Synthesis, Biophysical Characterization and <i>in Vitro</i>Transfection Activity of Novel Bivalent Amine Cationic Lipids in the Absence of Dioleoylphosphatidylethanolamine (DOPE)

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Pharmacology & pharmacy 2014年第11期5卷 1015-1028页

作者： Addai-Mensah Donkor Micheal Spelios Michalakis Savva Division of Pharmaceutical sciences Arnold & Marie Schwartz College of Pharmacy and Health Sciences Long Island University New York USA Faculty of Applied sciences Department of Applied Chemistry and Biochemistry University for Development Studies Navrongo Campus Upper East Region Ghana

In this paper, a novel series of bis [(aminoethyl)]-amine cationic lipid derivatives have been synthesized and identified to purity by NMR and Elemental analysis. B16-F0 cells were transfected with cationic lipid/pEGFP-N1 and cationic lipid/ß-gal lipoplexes complexed at +/- charge ratios of 1:1, 2:1, and 4:1. Dimyristoyl derivative showed highest activity at charge ratio 2:1 and both dimyristoyl and dioleoyl derivatives showed similar ß-gal activity at charge ratios 4:1. In 40 mM tris buffer pH 7.2 the dioleoyl derivative was able to fully complex with and retard pDNA at charge ratios above 2:1. None of the other lipid derivatives, dilauroyl, dimyristoyl, dipalmitoyl and distearoyl were able to fully neutralize the plasmid DNA at charge ratios similar to those used in the transfection experiment. The gel-to-liquid phase transition temperatures for dimyristoyl, dipalmitoyl and distearoyl were determined by a fluorescence anisotropy method to be 27.5°C, 32.5°C and 39°C, respectively. A gel-to-liquid crystalline phase transition temperature below 37°C, appears to be the crucial property that cationic lipids have to possess in order to mediate high levels of in vitro transfection activity in the absence of other helper lipids.

关键词： Gene Delivery Cationic Lipid Acyl Chain Fluidity Elasticity Lipoplex Transfection Non-Viral Vector DOPE Endosomal Release TNS

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Dynamic epi-transcriptomic landscape mapping with disease progression in estrogen receptor-positive breast cancer

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Cancer Communications 2023年第5期43卷 615-619页

作者： Stephen Keelan Mihaela Ola Sara Charmsaz Sinéad Cocchiglia Daniela Ottaviani Seán Hickey Siobhan Purcell Fiona Bane Aisling Hegarty Ben Doherty Katherine Sheehan Lance Hudson Nicola Cosgrove Benjamin Roux Muriel Laine Geoffrey Greene Damir Varešlija arnold Konrad Hill Leonie Young Endocrine Oncology Research Group Department of SurgeryRoyal College of Surgeons in IrelandUniversity of Medicine and Health SciencesDublinIreland Department of Surgery Beaumont HospitalDublinIreland Department of Pathology Beaumont HospitalDublinIreland Ben May Department for Cancer Research Department of Biochemistry and Molecular BiologyThe University of ChicagoChicagoILUSA The School of pharmacy and Biomolecular sciences The Royal College of Surgeons University of Medicine and Health SciencesDublinIreland Beaumont Royal college of Surgeons in Ireland Cancer Centre Beaumont HospitalDublinIreland

Dear Editor,The molecular determinants that drive breast cancer progression to metastasis are complex and partly controlled by nucleic acid epi-modifications[1].Although DNA-methyl modifications in breast cancer metastasis have been well described,there is limited understanding of the role of RNA methylation in advanced disease[2].This study aimed to provide an understanding on the role of the epitranscriptome in estrogen receptor-positive(ER+)breast cancer progression to metastasis.

关键词： breast metastasis cancer

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2,3-Diaryl-3H-imidazo[4,5-b]pyridine derivatives as potential anticancer and anti-inflammatory agents

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Acta Pharmaceutica Sinica B 2017年第1期7卷 73-79页

作者： Erin marie Kirwen Tarun Batra Chandrabose Karthikeyan Girdhar Singh Deora Vandana Rathore Chaitanya Mulakayala Naveen Mulakayala Amy Catherine Nusbaum Joel Chen Haneen Amawi Kyle Mc Intosh Sahabjada Neelam Shivnath Deepak Chowarsia Nisha Sharma Md Arshad Piyush Trivedi Amit KTiwari Department of Pharmacology and Experimental Therapeutics College of Pharmacy & Pharmaceutical SciencesUniversity of Toledo School of Pharmaceutical sciences Rajiv Gandhi Technical University The University of Queensland School of Pharmacy Dr. Reddy’s Institute of Life sciences University of Hyderabad Campus The University of Queensland School of Biomedical Sciences Department of Biosciences Sri Satya Sai Institute of Higher LearningAnantapur campus Clearsynth Labs Ltd. Research CentreIDA-Mallapur Molecular Endocrinology Lab Department of ZoologyUniversity of Lucknow University Institute of pharmacy Chhatrapati Shahu Ji Maharaj University

In this study we examined the suitability of the 3H-imidazo[4,5-b]pyridine ring system in developing novel anticancer and anti-inflammatory agents incorporating a diaryl pharmacophore. Eight 2,3-diaryl-3H-imidazo[4,5-b]pyridine derivatives retrieved from our in-house database were evaluated for their cytotoxic activity against nine cancer cell lines. The results indicated that the compounds showed moderate cytotoxic activity against MCF-7, MDA-MB-468, K562 and SaOS2 cells, with K562 being the most sensitive among the four cancer cell lines. The eight 2,3-diaryl-3H-imidazo[4,5-b]pyridine derivatives were also evaluated for their COX-1 and COX-2 inhibitory activity in vitro. The results showed that compound 3f exhibited 2-fold selectivity with IC_(50) values of 9.2 and 21.8 mmol/L against COX-2 and COX-1, respectively. Molecular docking studies on the most active compound 3f revealed a binding mode similar to that of celecoxib in the active site of the COX-2 enzyme.

关键词： 3H-Imidazo[4,5-b]pyridine Cytotoxicity MTT assay COX inhibitors Docking studies

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Nicotine-induced adrenal beta-arrestin1 upregulation mediates tobacco-related hyperaldosteronism leading to cardiac dysfunction

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World Journal of Cardiology 2020年第5期12卷 192-202页

作者： Natalie Cora Jennifer Ghandour Celina marie Pollard Victoria Lynn Desimine Krysten Elaine Ferraino Janelle marie Pereyra Rachel Valiente Anastasios Lymperopoulos Laboratory for the Study of Neurohormonal Control of the Circulation Department of Pharmaceutical Sciences(Pharmacology)College of PharmacyNova Southeastern UniversityFort LauderdaleFL 33328-2018United States

BACKGROUND Tobacco-related products,containing the highly addictive nicotine together with numerous other harmful toxicants and carcinogens,have been clearly associated with coronary artery disease,heart failure,stroke,and other heart *** the mechanisms by which nicotine contributes to heart disease is elevation of the renin-angiotensin-aldosterone system(RAAS)***,and its major metabolite in humans cotinine,have been reported to induce RAAS activation,resulting in aldosterone elevation in *** has various direct and indirect adverse cardiac *** is produced by the adrenal cortex in response to angiotensin II(AngII)activating AngII type 1 *** activity increases in chronic smokers,causing raised aldosterone levels(nicotine exposure causes the same in rats).AngII receptors exert their cellular effects via either G proteins or the twoβarrestins(βarrestin1 and-2).AIM Since adrenal?arrestin1 is essential for adrenal aldosterone production and nicotine/cotinine elevate circulating aldosterone levels in humans,we hypothesized that nicotine activates adrenal?arrestin1,which contributes to RAAS activation and heart disease *** We studied human adrenocortical zona glomerulosa H295R cells and found that nicotine and cotinine upregulateβarrestin1 mRNA and protein levels,thereby enhancing AngII-dependent aldosterone synthesis and *** In contrast,siRNA-mediatedβarrestin1 knockdown reversed the effects of nicotine on AngII-induced aldosterone production in H295 R ***,nicotine promotes hyperaldosteronism via adrenalβarrestin1,thereby precipitating cardiac dysfunction,also in vivo,since nicotine-exposed experimental rats with adrenal-specificβarrestin1 knockdown display lower circulating aldosterone levels and better cardiac function than nicotine-exposed control animals with normal adrenalβarrestin1 *** Adrenalβarrestin1 upregulation is one of the mechanisms by whic

关键词： Adrenocortical zona glomerulosa cell Aldosterone βarrestin Nicotine Signal transduction Tobacco-related heart disease

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SARS-CoV-2, surgeons and surgical masks

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World Journal of Clinical Cases 2021年第10期9卷 2170-2180页

作者： Mohammad Ibrahim Khalil Gouri Rani Banik Sarab Mansoor Amani S Alqahtani Harunor Rashid Department of Surgery Dhaka Medical College HospitalDhaka 1000Bangladesh Clinical Research Unit The Department of MedicineUniversity of New South WalesSydney 2217New South WalesAustralia National Centre for Immunisation Research and Surveillance The Children’s Hospital at Westmead and the University of SydneyWestmead 2145New South WalesAustralia The University of Sydney School of pharmacy Faculty of Medicine and HealthThe University of SydneySydney 2006New South WalesAustralia Research Department Saudi Food and Drug AuthorityRiyadh 13312Saudi Arabia National Centre for Immunisation Research and Surveillance The Children's Hospital at Westmeadand the University of SydneyWestmead 2145New South WalesAustralia Discipline of Child and Adolescent health the Faculty of Medicine and HealthThe University of SydneySydney 2145New South WalesAustralia marie Bashir Institute for Infectious Diseases and Biosecurity School of Biological Sciences and Sydney Medical SchoolThe University of SydneyWestmead 2145New South WalesAustralia

The exact risk association of coronavirus disease 2019(COVID-19)for surgeons is not quantified which may be affected by their risk of exposure and individual *** objective of this review is to quantify the risk of COVID-19 among surgeons,and explore whether facemask can minimise the risk of COVID-19 among surgeons.A systematised review was carried out by searching MEDLINE to locate items on severe acute respiratory syndrome coronavirus 2 or COVID-19 in relation to health care workers(HCWs)especially those work in surgical specialities including surgical nurses and ***,systematic reviews that assessed the effectiveness of facemask against viral respiratory infections,including COVID-19,among HCWs were *** from identified articles were abstracted,synthesised and *** primary studies that provided data on severe acute respiratory syndrome coronavirus 2 infection or experience among surgeons and 11 systematic reviews that provided evidence of the effectiveness of facemask(and other personal protective equipment)were *** the risk of COVID-19 could not be quantified precisely among surgeons,about 14%of HCWs including surgeons had COVID-19,there could be variations depending on *** was found to be somewhat protective against COVID-19,but the HCWs’compliance was highly variable ranging from zero to 100%.Echoing surgical societies’guidelines we continue to recommend facemask use among surgeons to prevent COVID-19.

关键词： COVID-19 health care worker Personal protective equipment SARS-CoV-2 Surgeon Surgical mask

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Comprehensive functional annotation of susceptibility variants identifies genetic heterogeneity between lung adenocarcinoma and squamous cell carcinoma

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Frontiers of Medicine 2021年第2期15卷 275-291页

作者： Na Qin Yuancheng Li Cheng Wang Meng Zhu Juncheng Dai Tongtong Hong Demetrius Albanes Stephen Lam Adonina Tardon Chu Chen Gary Goodman Stig EBojesen Maria Teresa Landi Mattias Johansson Angela Risch H-Erich Wichmann Heike Bickeboller Gadi Rennert Susanne arnold Paul Brennan John KField Sanjay Shete Loic Le Marchand Olle Melander Hans Brunnstrom Geoffrey Liu Rayjean JHung Angeline Andrew Lambertus AKiemeney Shan Zienolddiny Kjell Grankvist Mikael Johansson Neil Caporaso Penella Woll Philip Lazarus Matthew BSchabath Melinda CAldrich Victoria LStevens Guangfu Jin David CChristiani Zhibin Hu Christopher IAmos Hongxia Ma Hongbing Shen Department of Epidemiology Center for Global HealthSchool of Public HealthNanjing Medical UniversityNanjing 211166China State Key Laboratory of Reproductive Medicine Center for Global HealthNanjing Medical UniversityNanjing 211166China Department of Bioinformatics School of Biomedical Engineering and InformaticsNanjing Medical UniversityNanjing 211166China Jiangsu Key Lab of Cancer Biomarkers Prevention and TreatmentCollaborative Innovation Center for Cancer MedicineNanjing Medical UniversityNanjing 211166China China International Cooperation Center for Environment and Human health School of Public HealthNanjing Medical UniversityNanjing 211166China Division of Cancer Epidemiology and Genetics National Cancer InstituteBethesdaMD 20892-9304USA Department of Integrative Oncology British Columbia Cancer AgencyVancouverBC V5Z 1L3Canada Faculty of Medicine University of Oviedo and CIBERESPOviedo 33006Spain Program in Epidemiology Public Health Sciences DivisionFred Hutchinson Cancer Research CenterSeattleWA 98109-1024USA Public health sciences Division Swedish Cancer InstituteSeattleWA 98026USA Department of Clinical Biochemistry Copenhagen University HospitalCopenhagen DK-1017Denmark National Cancer Institute BethesdaMD 20892-9304USA Genetic Epidemiology Group International Agency for Research on CancerLyon 69372France Cancer Center Cluster Salzburg at PLUS Department of Molecular BiologyUniversity of SalzburgHeidelberg 5020Austria Institute of Medical Informatics Biometry and EpidemiologyChair of EpidemiologyLudwig Maximilians UniversityMunichBavaria 80539Germany Department of Genetic Epidemiology University Medical Center GoettingenGoettingen 37075Germany Technion Faculty of Medicine Carmel Medical CenterHaifa 3448516Israel Markey Cancer Center University of KentuckyLexingtonKY 40506-0054USA Department of Molecular and Clinical Cancer Medicine Roy Castle Lung Cancer Research ProgrammeThe University of Liverpool Institute of Translational MedicineLiverpool L697Z

Although genome-wide association studies have identified more than eighty genetic variants associated with non-small cell lung cancer(NSCLC)risk,biological mechanisms of these variants remain largely *** integrating a large-scale genotype data of 15581 lung adenocarcinoma(AD)cases,8350 squamous cell carcinoma(SqCC)cases,and 27355 controls,as well as multiple transcriptome and epigenomic databases,we conducted histology-specific meta-analyses and functional annotations of both reported and novel susceptibility *** identified 3064 credible risk variants for NSCLC,which were overrepresented in enhancer-like and promoter-like histone modification peaks as well as DNase I hypersensitive *** factor enrichment analysis revealed that USF1 was AD-specific while CREB1 was *** annotation and genebased analysis implicated 894 target genes,including 274 specifics for AD and 123 for SqCC,which were overrepresented in somatic driver genes(ER=1.95,P=0.005).Pathway enrichment analysis and Gene-Set Enrichment Analysis revealed that AD genes were primarily involved in immune-related pathways,while SqCC genes were homologous recombination deficiency *** results illustrate the molecular basis of both wellstudied and new susceptibility loci of NSCLC,providing not only novel insights into the genetic heterogeneity between AD and SqCC but also a set of plausible gene targets for post-GWAS functional experiments.

关键词： lung cancer genome-wide association study function annotation immune homologous recombination repair deficiency genetic heterogeneity

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Role of endoscopic ultrasound in the characterization of solid pseudopapillary neoplasm of the pancreas

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World Journal of Gastrointestinal Endoscopy 2023年第4期15卷 273-284页

作者： Katarzyna M Pawlak Nadeem Tehami Ben Maher Shujaath Asif Krishn Kant Rawal Daniel Vasile Balaban Mohammed Tag-Adeen Fahd Ghalim Wael A Abbas Elsayed Ghoneem Khaled Ragab Mahmoud El-Ansary Shanil Kadir Sunil Amin Keith Siau Anna Wiechowska-Kozlowska Klaus Mönkemüller Dalia Abdelfatah Abeer Abdellatef Sundeep Lakhtakia Hussein Hassan Okasha Endoscopy Unit Department of GastroenterologyHospital of The Ministry of Interior and AdministrationSzczecin 01-218Poland Interventional Endoscopy Unit University Hospital Southampton NHS Foundation Trust3AX POUnited Kingdom Consultant Gastroenterologist AIG HospitalsHyderabad 500032India Department of Gastroenterology Prime Institute of Digestive SciencesRajkot 360001India Department of Gastroenterology Central Military Emergency University HospitalCarol Davila University of Medicine and PharmacyBucharest 010011Romania Division of Gastroenterology and Hepatology Department of Internal MedicineQena Faculty of MedicineSouth Valley UniversityQena 83511Egypt Department of Endoscopy Shefa Al-Orman HospitalLuxor 85951Egypt Interventional Endoscopy Unit Sainte Marie HospitalOSNY 95520France Department of Internal Medicine Gastroenterology UnitFaculty of MedicineAssuit UniversityAssuit 71511Egypt Department of Gastroenterology and Hepatology Faculty of MedicineMansoura UniversityMansoura 35511Egypt Department of Hepatology and Gastroenterology Theodor Bilharz Research InstituteGiza 12511Egypt Department of Hepatology&Gastroenterology Theodor Bilharz Research InstituteGiza 12511Egypt Department of Gastroenterology Liaquat National Hospital&Medical CollegeKarachi 75900Pakistan

BACKGROUND Solid pseudopapillary neoplasm(SPN)is an uncommon pathology of the pancreas with unpredictable malignant *** ultrasound(EUS)assessment plays a vital role in lesion characterization and confirmation of the tissue ***,there is a paucity of data regarding the imaging assessment of these *** To determine the characteristic EUS features of SPN and define its role in preoperative *** This was an international,multicenter,retrospective,observational study of prospective cohorts from 7 large hepatopancreaticobiliary *** cases with postoperative histology of SPN were included in the *** collected included clinical,biochemical,histological and EUS *** One hundred and six patients with the diagnosis of SPN were *** mean age was 26 years(range 9 to 70 years),with female predominance(89.6%).The most frequent clinical presentation was abdominal pain(80/106;75.5%).The mean diameter of the lesion was 53.7 mm(range 15 to 130 mm),with the slight predominant location in the head of the pancreas(44/106;41.5%).The majority of lesions presented with solid imaging features(59/106;55.7%)although 33.0%(35/106)had mixed solid/cystic characteristics and 11.3%(12/106)had cystic *** was observed in only 4(3.8%)*** pancreatic duct dilation was uncommon,evident in only 2 cases(1.9%),whilst common bile duct dilation was observed in 5(11.3%)*** patient demonstrated a double duct sign at *** and Doppler evaluation demonstrated inconsistent appearances with no emergence of a predictable *** guided biopsy was performed using three different types of needles:Fine needle aspiration(67/106;63.2%),fine needle biopsy(37/106;34.9%),and Sonar Trucut(2/106;1.9%).The diagnosis was conclusive in 103(97.2%)***-seven patients were treated surgically(91.5%)and the post-surgical SPN diagnosis was confirmed in all *** the 2-year

关键词： Solid pseudopapillary neoplasm SPN Frantz tumor Endoscopic ultrasound features EUSguided biopsy Fine needle aspiration/biopsy

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