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简介：Objective:ToexaminetheexpressionsofMDM2,P53andP27proteinsinchronicesophagitis,para-cancermucosaandesophagealcarcinoma.Methods:ImmunohistochemistrywasusedtodetecttheexpressionsofMDM2,P53andP27proteinsinforty-sevenpatientssufferingfromchronicesophagitisandeighty-fivecasesofesophagealcarcinomaandcorrespondingpara-cancermucosa.Flowcytometry((FCM)wasappliedtodetectthequantitiesoftheseproteinsexpressedinfreshtissuesof48casesofesophagealcancerandtheirpara-cancertissuesand24casesofrelativenormalmucosaatthesurfaceofcuttingedge.Results:Immunohistochemistryresultsshowedthattheexpressionsofthethreestudiedproteinswereverysimilarintheepitheliaofchronicesophagitisandpara-cancermucosa(P>0.05).BoththequalitativeandquantitativestudiesdisplayedthattheP53proteinhadnoexpressionanditsaccumulationswouldappearonlyintheearlystagesofesophaguscancerationwhiletheMDM2andP27proteinshaddifferentdegreesofexpressionsincasesofnormalesophagealmucosa.MDM2proteinmarkedlyincreasedintheadvancedstagesofesophagealcanceration.AquantitativestudyshowedthattheexpressionofP27proteinhadalinearityofdecreasingtendency(F=9.132,P=0.002)inthecourseofesophagealcanceration.Conclusion:Chronicesophagitismaybeaprecancerouslesion.OwingtothechangesoftheP53andP27proteins,wecanalsoconcludethattheseoccurintheearlystagesofesophagusoncogenesis,howeverthechangesofMDM2expressionmayoccurintheadvancedstageofesophagealcanceration.

简介：AbstractBackground:Esophageal squamous cell carcinoma (ESCC) is one of the most aggressive cancers without effective therapy. To explore potential molecular targets in ESCC, we quantified the mutation spectrum and explored the relationship between gene mutation and clinicopathological characteristics and programmed death-ligand 1 (PD-L1) expression.Methods:Between 2015 and 2019, 29 surgically resected ESCC tissues and adjacent normal tissues from the Fourth Hospital of Hebei Medical University were subjected to targeted next-generation sequencing. The expression levels of PD-L1 were detected by immunohistochemistry. Mutational signatures were extracted from the mutation count matrix by using non-negative matrix factorization. The relationship between detected genomic alterations and clinicopathological characteristics and PD-L1 expression was estimated by Spearman rank correlation analysis.Results:The most frequently mutated gene was TP53 (96.6%, 28/29), followed by NOTCH1 (27.6%, 8/29), EP300 (17.2%, 5/29), and KMT2C (17.2%, 5/29). The most frequently copy number amplified and deleted genes were CCND1/FGF3/FGF4/FGF19 (41.4%, 12/29) and CDKN2A/2B (10.3%, 3/29). By quantifying the contribution of the mutational signatures to the mutation spectrum, we found that the contribution of signature 1, signature 2, signature 10, signature 12, signature 13, and signature 17 was relatively high. Further analysis revealed genetic variants associated with cell cycle, chromatin modification, Notch, and Janus kinase-signal transducer and activator of transcription signaling pathways, which may be key pathways in the development and progression of ESCC. Evaluation of PD-L1 expression in samples showed that 13.8% (4/29) of samples had tumor proportion score ≥1%. 17.2% (5/29) of patients had tumor mutation burden (TMB) above 10 mut/Mb. All samples exhibited microsatellite stability. TMB was significantly associated with lymph node metastasis (r = 0.468, P = 0.010), but not significantly associated with PD-L1 expression (r = 0.246, P = 0.198). There was no significant correlation between PD-L1 expression and detected gene mutations (all P > 0.05).Conclusion:Our research initially constructed gene mutation profile related to surgically resected ESCC in high-incidence areas to explore the mechanism underlying ESCC development and potential therapeutic targets.

简介：ＴＨＥＥＦＦＥＣＴＯＦＲＥＴＩＮＯＩＣＡＣＩＤＯＮＣＥＬＬＭＥＭＢＲＡＮＥＡＮＤＭＥＴＡＳＴＡＴＩＣＡＢＩＬＩＴＹＯＦＭＯＵＳＥＦＯＲＥＳＴＯＭＡＣＨＣＡＲＣＩＮＯＭＡＣＥＬＬＹｕＸｉａｏｄａｎ于晓；ＺｈａｏＸｕｅｍｅｉ赵雪梅；ＧａｏＪｉｎ高进（Ｉｎ...

简介：Objective:Livermetastasis,whichcontributessubstantiallytohighmortality,isthemostcommonrecurrentmodeofcoloncarcinoma.Thus,itisnecessarytoidentifygenesimplicatedinmetastaticcolonizationoftheliverincoloncarcinoma.Methods:WecomparedmRNAprofilingin18normalcolonmucosa(N),20primarytumors(T)and19livermetastases(M)samplesfromthedatasetGSE49355andGSE62321ofGeneExpressionOmnibus(GEO)database.Geneontology(GO)andpathwaysoftheidentifiedgeneswereanalyzed.Co-expressionnetworkandproteinproteininteraction(PPI)networkwereemployedtoidentifytheinteractionrelationship.SurvivalanalysesbasedonTheCancerGenomeAtlas(TCGA)databasewereusedtofurtherscreening.Then,thecandidategeneswerevalidatedbyourdata.Results:Weidentified22specificgenesrelatedtolivermetastasisandtheywerestronglyassociatedwithcellmigration,adhesion,proliferationandimmuneresponse.Simultaneously,theresultsshowedthatC-X-Cmotifchemokineligand14(CXCL14)mightbeafavorablepredictionfactorforsurvivalofpatientswithcoloncarcinoma.Importantly,ourvalidateddatafurthersuggestedthatlowerCXCL14representedpooreroutcomeandcontributedtometastasis.Genesetenrichmentanalysis(GSEA)showedthatCXCL14wasnegativelyrelatedtotheregulationofstemcellproliferationandepithelialtomesenchymaltransition(EMT).Conclusions:CXCL14wasidentifiedasacrucialanti-metastasisregulatorofcoloncarcinomaforthefirsttime,andmightprovidenoveltherapeuticstrategiesforcoloncarcinomapatientstoimproveprognosisandpreventmetastasis.

简介：AIM:ToexploreexpressionsofPIK3CAintheprogressionofgastriccancerfromprimarytometastasisanditseffectsonactivationofphosphatidylinositol3-kinase(PI3K)/Aktpathway.METHODS:mRNAandproteinlevelsofPIK3CAwereassessed,respectively,byreal-timequantitativepolymerasechainreactionandimmunohistochemistryinspecimensofnormalgastricmucosa,primaryfociandlymphnodeanddistantmetastasisofgastriccancer.AktandphosphorylatedAktproteinwerealsoexaminedbyWesternblottinginthesetissues,inordertoanalyzetheeffectofPIK3CAexpressionlevelchangesontheactivationofPI3K/Aktsignalingpathway.RESULTS:PIK3CAmRNAinlymphnodemetastasiswereapproximately5and2foldshigher,respectively,thanthatinthecorrespondingnormalgastricmucosaandprimarygastriccancertissues(P<0.05),whilenostatisticalsignificancewasfoundcomparedwithdistantmetastasis.Immunohistochemically,PIK3CAproteinexpressionwasdiscoveredin7(35%)specimensof20primaryfocivs10(67%)of15oflymphnodemetastasisor11(61%)of18ofdistantmetastasis(35%vs67%,P=0.015;35%vs61%,P=0.044).WiththeincreasedlevelofPIK3CAexpression,thetotalAktproteinexpressionremainedalmostunchanged,butp-Aktproteinwasupregulatedmarkedly.CONCLUSION:IncreasedexpressionofPIK3CAisexpectedtobeapromisingindicatorofmetastasisingastriccancer.Up-regulationofPIK3CAmaypromotethemetastasisofgastriccancerthroughaberrantactivationofPI3K/Aktsignaling.

简介：AbstractObjective:We present the largest population based study of sinonasal squamous cell carcinoma (SCC) to identify risk factors for presentation with nodal metastasis.Methods:The National Cancer Database (NCDB) was used for this study. Location codes corresponding to the nasal cavity and paranasal sinuses and histology codes representing SCC malignancy were queried. Logistic regression analysis was performed to identify factors associated with presentation with nodal metastasis.Results:6448 cases met inclusion criteria. Nodal metastasis at presentation was seen in 13.2% of patients, with the sinus subsite (19.3%) being a significant risk factor for nodal metastasis at presentation when compared to the nasal cavity (7.9%). Logistic regression analysis showed black, uninsured and Medicaid patients were more likely than white and privately insured patients, respectively, to present with nodal metastasis.Conclusions:In sinonasal SCC, the sinus subsite has a significantly increased risk of nodal metastasis compared to the nasal cavity. Black race, uninsured and Medicaid patients are more likely to have nodal metastasis at presentation.

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简介：AbstractTumor biomarkers play important roles in tumor growth, invasion, and metastasis. Imaging of specific biomarkers will help to understand different biological activities, thereby achieving precise medicine for each head and neck squamous cell carcinoma (HNSCC) patient. Here, we describe various molecular targets and molecular imaging modalities for HNSCC imaging. An extensive search was undertaken in the PubMed database with the keywords including "HNSCC," "molecular imaging," "biomarker," and "multimodal imaging." Imaging targets in HNSCC consist of the epidermal growth factor receptor, cluster of differentiation 44 variant 6 (CD44v6), and mesenchymal-epithelial transition factor and integrins. Targeted molecular imaging modalities in HNSCC include optical imaging, ultrasound, magnetic resonance imaging, positron emission tomography, and single-photon emission computed tomography. Making the most of each single imaging method, targeted multimodal imaging has a great potential in the accurate diagnosis and therapy of HNSCC. By visualizing tumor biomarkers at cellular and molecular levels in vivo, targeted molecular imaging can be used to identify specific genetic and metabolic aberrations, thereby accelerating personalized treatment development for HNSCC patients.

简介：Objective:Differentiatedthyroidcarcinomas(DTCs)areclassifiedintopapillarythyroidcarcinoma(PTC)andfollicularthyroidcarcinoma(FTC).DTCsareanalyzedasasinglegroupinclinicalstudiesthatinvestigatedtheprognosticfactorsandprognosisofthesemalignancies.However,thebiologicalbehaviorsofthesecarcinomassignificantlydiffer.Inthepresentstudy,weaimedtodetectdifferencesintheoutcomesbetweenPTCandFTCinMansouraUniversityHospitalinEgypt.Methods:Atotalof558patientswithhistologicallyproventhyroidcarcinomasfromJanuary2003toDecember2012wereretrospectivelyenrolled.Theclinicalandpathologicaldataofpatientswerereviewed.Results:Largeprimarytumorsize,lymphnodeinvolvement,extrathyroidextension,anddistantmetastasisweresignificantpoorprognosticfactorsforoverallsurvival(OS)inoldPTCpatients.Coxhazardanalysisshowedthatthepatient'sage,extrathyroidextension,anddistantmetastasisweretheonlyindependentprognosticfactors.InFTCpatients,onlythedistantmetastasisanddegreeoftumorinvasionweresignificantpoorprognosticfactorsinOSunivariateanalysis.However,thesefactorswerenonsignificantinmultivariateanalysis.The10-yearOSrateswere97%and89%forPTCandFTC,respectively(P=0.003).The10-yeardisease-freesurvival(DFS)rateswere77.2%inPTCvs.65%inFTC(P=0.179).Conclusion:ThesignificantprognosticfactorsvarybetweenthetwotypesofDTCs.Therefore,PTCandFTCpatientsneedtobeanalyzedandreportedindependently.PTCsurvivaliswidelyandsignificantlyaffectedbyage,extrathyroidextension,anddistantmetastasis.Bycontrast,thesefactorswerenonsignificantinFTC,whichshowedpoorersurvivalthanPTC.

简介：AbstractBackground:Accumulating evidence has revealed that circulating microRNAs (miRNAs) can serve as non-invasive biomarkers for cancer diagnosis. This study aimed to identify differentially expressed miRNAs in serum which might become potential biomarkers for non-invasive diagnosis of papillary thyroid carcinoma (PTC).Methods:The experiment was carried out between 2015 and 2017. In the screening stage, the Exiqon miRNA quantitative real-time polymerase chain reaction (qPCR) panel was applied to select candidate miRNAs. In the following training, testing, and external validation stages, the serum samples of 100 patients and 96 healthy controls (HCs) were analyzed to compare the expression levels of the identified miRNAs. The areas under the receiver operating characteristic curves (AUCs) were calculated to assess the diagnostic value of the identified signature.Results:Three miRNAs (miR-25-3p, miR-296-5p, and miR-92a-3p) in serum were consistently up-regulated in PTC patients compared with HCs. A three-miRNA panel was constructed by logistic regression analysis and showed better diagnostic performance than a single miRNA for PTC detection. The AUCs of the panel were 0.727, 0.771, and 0.862 for the training, testing, and external validation stage, respectively. Meanwhile, the panel showed stable capability in differentiating PTC patients from patients with benign goiters, with an AUC as high as 0.969. For further exploration, the three identified miRNAs were analyzed in tissue samples (23 PTC vs. 23 HCs) and serum-derived exosomes samples (24 PTC vs. 24 HCs), and the altered expression in the tumor also indicated their close relationship with PTC disease.Conclusion:We identify a three-miRNA panel in serum which might serve as a promising biomarker for PTC diagnosis.

简介：ＥＸＰＲＥＳＳＩＯＮＯＦＥＢＶＬＡＴＥＮＴＭＥＭＢＲＡＮＥＰＲＯＴＥＩＮＩＮＥＳＯＰＨＡＧＥＡＬＣＡＲＣＩＮＯＭＡＡＮＤＰＡＲＡＣＡＮＣＥＲＯＵＳＭＵＣＯＳＡＷｕＭｉｎｇｙａｏ吴名耀ＬｉａｎｇＹｉｎｇｒｕｉ梁英锐ＷｕＸｉａｎｙｉｎｇ吴贤英Ｄｅｐａｒ...

简介：AbstractBackground:Circular RNA ciRS-7 has been reported to be involved in the progression of various cancers. However, ciRS-7 expression and its role in clear cell renal cell carcinoma (ccRCC) progression remains unclear. This study aimed to investigate the effect of ciRS-7 expression on ccRCC and the related signaling pathway.Methods:ciRS-7 expression was analyzed using quantitative reverse transcription polymerase chain reaction in 87 pairs of ccRCC and matched adjacent normal tissues. The role of ciRS-7 in ccRCC cell proliferation and invasion was determined using the cell counting kit-8 and invasion assays, respectively. Potential mechanisms underlying the role of ciRS-7 in promoting ccRCC progression were explored by Western blotting. The relationship between the expression of ciRS-7 and features of ccRCC was analyzed by the Chi-square test and progression-free survival was determined using a Kaplan-Meier plot.Results:ciRS-7 was overexpressed in ccRCC tissues compared with that in matched adjacent normal tissues. In addition, ciRS-7 up-regulation was closely associated with tumor diameter (P = 0.050), clinical stage (P = 0.009), and distant metastasis (P = 0.007). ciRS-7 knockdown in 786O and 769P cells markedly inhibited their proliferative and invasive abilities. In addition, ciRS-7 inhibition reduced phosphorylated epidermal growth factor receptor (p-EGFR) and phosphorylated serine/threonine kinase (p-Akt) levels.Conclusions:ciRS-7 up-regulation could promote ccRCC cell proliferation and invasion, which may be related with the EGFR/Akt signaling pathway. ciRS-7 might be a potential ccRCC therapeutic target.

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简介：Breastcancerisoneofthemostcommonmalignanciesamongwomenanditsmorbidityhasrecentlyincreasedinmanypartsoftheworld[1].Numerousfactorshavebeenreportedtobeassociatedwithdevelopmentofbreastcancerincludingangiogenesis.Angiogenesisortheformationofnewbloodvesselnetworks,notonlyplaysapivotalroleinhumannormaldevelopment,butalsoinpathophysiologicalconditionssuchasinflammatorydiseasesandneoplasms[2]

简介：Objective:Patientswithheadandneckcanceroftensufferfrommalnutrition.Thisstudyaimstoinvestigatetheinfluenceofbodymassindex(BMI)ontheprognosisoflaryngealsquamouscellcarcinoma(LSCC).Methods:Atotalof473patientswithLSCCinitiallytreatedatSunYat-senUniversityCancerCenterbetweenJanuary2005andJuly2009wereretrospectivelyreviewed.SurvivalanalysiswasperformedbytheKaplan-MeiermethodandCoxregressionmodel.Results:LowBMIbeforetreatmentwassignificantlyassociatedwithpooroverallsurvivalinpatientswithLSCC(P<0.001).BMIwasanindependentprognosticfactorforpatientswithLSCC.Conclusion:LeannessbeforetreatmentwasassociatedwithpoorprognosisinpatientswithLSCC.GoodnutritionalstatusisfavorabletoimprovesurvivalinpatientswithLSCC.

简介：Objective:Inthisstudy,weexaminetheeffectsofrecombinantadenovirus-p53(rAd-p53)onthepancreaticcarcinomacelllineSW1990.Specifically,wedetermineifexpressionofrAd-p53sensitizesthesecellstoradiation.Methods:FollowingtransfectionofSW1990cellswithrAd-p53,wemeasuredexpressionofP53,P21andBaxbyimmunocytochemistry.Bothtransfectedandcontrolcelllineswereirradiatedwitharangeofdoses,andthesurvivalfractions(SF)werecalculated.Dosesurvivalcurveswereconstructedandmodeledforcomparison.Results:TransfectionofSW1990cellswithrAd-p53resultedinincreasedexpressionofP53,P21andBaxinatime-dependentmanner.At96haftertransfection,89.92%ofcellsexpressedP53,56.8%expressedP21,and76.50%expressedBax.TheSFfollowingradiationwaslowerintherAd-p53transfectedcellscomparedtothecontrolcells,suggestingthatrAd-p53sensitizesSW1990cellstoradiation(D0fortheexperimentalandcontrolgroupswas2.199and2.462,respectively).Conclusions:UseoftheadenoviralvectorisaneffectivemeansoftransfectingSW1990cellswithwild-typeP53,andthissensitizesthecelllinetoirradiation.ThisworksuggeststhatcombiningrAd-p53withradiationtherapyinpancreaticcancermaybetherapeuticallybeneficial.