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简介：AbstractBackground:Circulating tumor DNA (ctDNA) is a promising biomarker for non-invasive epidermal growth factor receptor mutations (EGFRm) detection in lung cancer patients, but existing methods have limitations in sensitivity and availability. In this study, we used the ΔCt value (mutant cycle threshold [Ct] value-internal control Ct value) generated during the polymerase chain reaction (PCR) assay to convert super-amplification-refractory mutation system (superARMS) from a qualitative method to a semi-quantitative method named reformed-superARMS (R-superARMS), and evaluated its performance in detecting EGFRm in plasma ctDNA in patients with advanced lung adenocarcinoma.Methods:A total of 41 pairs of tissues and plasma samples were obtained from lung adenocarcinoma patients who had known EGFRm in tumor tissue and were previously untreated. EGFRm in ctDNA was identified by using superARMS. Through making use of ΔCt value generated during the detection process of superARMS, we indirectly transform this qualitative detection method into a semi-quantitative PCR detection method, named R-superARMS. Both qualitative and quantitative analyses of the data were performed. Kaplan-Meier analysis was performed to estimate the progression-free survival (PFS) and overall survival (OS). Fisher exact test was used for categorical variables.Results:The concordance rate of EGFRm in tumor tissues and matched plasma samples was 68.3% (28/41). At baseline, EGFRm-positive patients were divided into two groups according to the cut-off ΔCt value of EGFRm set at 8.11. A significant difference in the median OS (mOS) between the two groups was observed (EGFRm ΔCt ≤8.11 vs. >8.11: not reached vs. 11.0 months; log-rank P = 0.024). Patients were divided into mutation clearance (MC) group and mutation incomplete clearance (MIC) group according to whether the ΔCt value of EGFRm test turned negative after 1 month of treatment. We found that there was also a significant difference in mOS (not reached vs. 10.4 months; log-rank P = 0.021) between MC group and MIC group. Although there was no significant difference in PFS between the two groups, the two curves were separated and the PFS of MC group tended to be higher than the MIC group (not reached vs. 27.5 months; log-rank P = 0.088). Furthermore, EGFRm-positive patients were divided into two groups according to the cut-off of the changes in ΔCt value of EGFRm after 1 month of treatment, which was set at 4.89. A significant difference in the mOS between the two groups was observed (change value of ΔCt >4.89 vs. ≤4.89: not reached vs. 11.0 months; log-rank P = 0.014).Conclusions:Detecting EGFRm in ctDNA using R-superARMS can identify patients who are more likely sensitive to targeted therapy, reflect the molecular load of patients, and predict the therapeutic efficacy and clinical outcomes of patients.

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简介：AbstractBackground:Due to development of magnetic resonance-based functional imaging, it is easier to detect micro-structural alterations of tumor tissues. The aim of this study was to conduct a preliminary evaluation of the correlation of non-Gaussian diffusion kurtosis imaging (DKI) parameters with expression of molecular markers (epidermal growth factor receptor [EGFR]; anaplastic lymphoma kinase [ALK]; Ki-67 protein) in patients with advanced lung adenocarcinoma, using routine diffusion-weighted imaging as the reference standard.Methods:Data from patients with primary lung adenocarcinoma diagnosed at Cancer Hospital, Chinese Academy of Medical Sciences (CHCAMS) from 2016 to 2019 were collected for retrospective analysis. The pathologic and magnetic resonance imaging data of 96 patients who met the inclusion criteria were included in this study. Specifically, the Kapp and Dapp parameters measured from the DKI model; apparent diffusion coefficient (ADC) value from the diffusion-weighted imaging model; and the EGFR, ALK, and Ki-67 biomarkers detected by immunohistochemistry and/or molecular biology techniques after biopsy or surgery were evaluated. The relations between quantitative parameters (ADC, Kapp, Dapp) and pathologic outcomes (EGFR, ALK, and Ki-67 expression) were analyzed by Spearman correlation test.Results:Of the 96 lung adenocarcinoma lesions (from 96 patients), the number of EGFR- and ALK-positive and high Ki-67 expressing lesions were 53, 12, and 83, respectively. The Kapp values were significantly higher among patients with EGFR-positive mutations (0.81 ± 0.12 vs. 0.66 ± 0.10, t = 6.41, P < 0.001), ALK rearrangement-negative (0.76 ± 0.12 vs. 0.60 ± 0.15, t = 4.09, P < 0.001), and high Ki-67 proliferative index (PI) (0.76 ± 0.12 vs. 0.58 ± 0.13, t = 4.88, P < 0.001). The Dapp values were significantly lower among patients with high Ki-67 PI (3.19 ± 0.69 μm2/ms vs. 4.20 ± 0.83 μm2/ms, t = 4.80, P < 0.001) and EGFR-positive mutations (3.11 ± 0.73 μm2/ms vs. 3.59 ± 0.77 μm2/ms, t = 3.12, P = 0.002). The differences in mean Dapp (3.73 ± 1.26 μm2/ms vs. 3.26 ± 0.68 μm2/ms, t = 1.96, P = 0.053) or ADC values ([1.34 ± 0.81] × 10-3 mm2/s vs. [1.33 ± 0.41] × 10-3 mm2/s, t = 0.07, P = 0.941) between the groups with or without ALK rearrangements were not statistically significant. The ADC values were significantly lower among patients with EGFR-positive mutation ([1.19 ± 0.37] × 10-3 mm2/s vs. [1.50 ± 0.53] × 10-3 mm2/s, t = 3.38, P = 0.001) and high Ki-67 PI ([1.28 ± 0.39] × 10-3 mm2/s vs. [1.67 ± 0.77] × 10-3 mm2/s, t = 2.88, P = 0.005). Kapp was strongly positively correlated with EGFR mutations (r = 0.844, P = 0.008), strongly positively correlated with Ki-67 PI (r = 0.882, P = 0.001), and strongly negatively correlated with ALK rearrangements (r = -0.772, P = 0.001). Dapp was moderately correlated with EGFR mutations (r = -0.650, P = 0.024) or Ki-67 PI (r = -0.734, P = 0.012). ADC was moderately correlated with Ki-67 PI (r = -0.679, P = 0.033).Conclusions:The Kapp value of DKI parameters was strongly correlated with different expression of EGFR, ALK, and Ki-67 in advanced lung adenocarcinoma. The results potentially indicate a surrogate measure of the status of different molecular markers assessed by non-invasive imaging tools.

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简介：在病原体识别的像使用费的受体(TLR)的角色在最近的年里是快速地先进的。然而，进在非传染的织物损害的TLR的功能的调查刚开始了。以前，我们和其它表明了那碎裂的hyaluronan(哈)在织物损害期间积累。CD44被要求在织物损害期间清除HA，并且损害了清理哈在不停的发炎的结果。另外，碎裂哈在损害地点由煽动性的房间刺激煽动性的基因的表示。最近，我们识别了那哈碎片要求TLR2和TLR4刺激老鼠巨噬细胞生产煽动性的chemokines和cytokines。在一个非传染的肺损害模型，在TLR2和TLR4缺乏的老鼠显示出煽动性的房间的损害transepithelial迁居，增加的织物损害，提高的肺上皮的房间apoptosis，和减少的幸存。在高分子的质量的表示上的肺上皮的房间哈对尖锐的肺损害和apoptosis的保护的老鼠，部分地通过NF-kappaB的TLR依赖的基础激活。在TLR2和TLR4的夸大的损害缺乏的老鼠看起来由于上皮的房间上的损害HA-TLR相互作用。这些研究识别那个主机矩阵部件哈并且TLR相互作用提供开始煽动性的回答的信号，维持上皮的房间完整，并且支持从尖锐的肺损害的恢复。房间研究(2006)16：693-701。做i：10.1038/sj.cr.7310085；出版联机2006年8月8日。

简介：Objective:Tocomparetheefficacyandadverseeffectsofpaclitaxel-etoposide-carboplatin/cisplatin(TEP/TCE)regimenwiththoseofetoposide-carboplatin/cisplatin(EP/CE)regimenasfirst-linetreatmentforcombinedsmall-celllungcancer(CSCLC).Methods:Aretrospectivestudywasconductedon62CSCLCpatientswhoweretreatedatTianjinMedicalUniversityCancerInstituteandHospitalfromJuly2000toApril2013andadministeredwithTEP/TCEregimen(n=19)orEP/CEregimen(n=43)asfirst-lineCSCLCtreatment.Allpatientsreceivedmorethantwocyclesofchemotherapy,andtheresponsewasevaluatedeverytwocycles.Theprimaryendpointwasoverallsurvival(OS),andthesecondaryendpointswereprogression-freesurvival(PFS),objectiveresponserate(ORR),diseasecontrolrate(DCR),andadverseeffects.Results:ORRbetweentheTEP/TCEandEP/CEgroupsshowedastatisticaldifference(90%vs.53%,P=0.033).BothgroupsfailedtoreachastatisticaldifferenceinDCR(100%vs.86%,P=0.212).ThemedianPFSandOSoftheTEP/TCEgroupwereslightlylongerthanthoseoftheEP/CEgroup,althoughbothgroupsfailedtoreachastatisticaldifference(10.5vs.8.9months,P=0.484;24.0vs.17.5months,P=0.457).However,stratifiedanalysisindicatedthatthePFSofpatientswithstagesIIIandIVCSCLCshowedmarginallysignificantdifferencebetweentheTEP/TCEandEP/CEgroups(19.5vs.7.6months;P=0.071).BothratesofgradeIVbonemarrowdepressionandterminationofchemotherapyintheTEP/TCEgroupweresignificantlyhigherthanthoseintheEP/CEgroup(26.3%vs.7.0%,P=0.036;31.6%vs.14.7%,P=0.004).Conclusion:TheTEP/TCEregimenmaynotbepreferredforCSCLC,andthisthree-drugregimenrequiresfurtherexplorationandresearch.Todate,theEP/CEregimenremainsthestandardtreatmentforCSCLCpatients.

简介：客观最近的证据建议Oct-4高度在几癌症被表示，并且它的表示贡献肿瘤生长。在这研究，我们在直肠的腺癌调查了Oct-4表示的水平，并且在这些情况中评估了Oct-4表示的预示的意义。Oct-4的immunohistochemical表达式在52件修理福尔马林的嵌入石蜡的手术后的直肠的腺癌织物样品被计算的方法。关于临床的结果的Oct-4的immunoreactivity的影响被Kaplan-Meier和木头等级决定。结果Oct-4的表示水平从0～18.5%。在Oct-4之间没有重要协会表示和性，年龄(P=0.123)，临床的阶段(P=0.391)，和组织学的等级(P=0.056)(P=0.772)。有Oct-4的否定、积极的表示的3年的本地没有复发的率是83.5%和75.0%，分别地(P=0.583)。有Oct-4的否定、积极的表示的3年的没有转移的率是88.6%和61.9%，分别地(P=0.035)。有Oct-4的否定、积极的表示的3年的全面幸存率是77.9%和49.0%，分别地(P=0.037)。结果建议那胚胎的干细胞标记Oct-4表情的结论可以与直肠的腺癌在病人有预示的意义。然而，更多和更大的研究被要求证实这。

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简介：Objective:Weinvestigatedthecorrelationbetweenthenumberofcirculatingtumorcells(CTCs)andwholebodymetabolictumorvolume(WBMTV)measuredby18F-fluorodeoxyglucose(FDG)positronemissiontomography/computedtomography(PET/CT).TheaimwastoevaluatethevalueoftheincorporationofCTCnumberandWBMTVintheprognosticpredictionofstageIIIsmall-celllungcancer(SCLC).Methods:Onehundredandtwenty-ninepatientswereenrolledinthisstudy.Allpatientsweretreatedwithfourcyclesofaplatinum-basedregimenandconcurrentchestirradiation,followedbyprophylacticcranialirradiation.BloodsamplesforCTCanalysiswereobtainedfrom112patientsbeforetheinitiationofchemotherapy(asabaseline),aftercycle1andaftercycle4.CTCsweremeasuredusingtheCELLSEARCH?system.ThepatientsunderwentpretreatmentFDGPET/CTWBMTV,whichincludedallmalignantlesions.TheSpearmanranktestwasusedtodeterminethecorrelationamongCTCcounts,WBMTVanddiseasestage.Overallsurvival(OS)andprogression-freesurvival(PFS)curveswereproducedusingtheKaplan-Meiermethod,andsurvivaldifferencesbetweengroupswereassessedbythelog-ranktest.Results:ThenumberofCTCsatbaselinedidnotcorrelatewithWBMTVbeforetheinitiationoftherapy(P=0.241).ThenumberofCTCsatbaselineandtheWBMTVbeforetheinitiationoftherapywereindependentrelevantfactorsforPFSandOS.Thesubgroupanalysis(GroupA:CTCcount>19.5andaWBMTV>266.5cm^3;GroupB:CTCcount>19.5andaWBMTV≤266.5cm^3;GroupC:CTCcount≤19.5andaWBMTV>266.5cm^3;GroupD:CTCcount≤19.5andaWBMTV≤266.5cm^3)showedthatthedifferenceswerestatisticallysignificantinthemedianPFS(GroupAvs.D,P<0.001;GroupBvs.D,P=0.018;GroupCvs.D,P=0.029)andinthemedianOS(GroupAvs.D,P<0.001;GroupBvs.D,P=0.012).Conclusions:CTCnumberandWBMTVarerelatedtoprogressionanddeathinpatientswithSCLC.TheincorporationofCTCnumberandWBMTVscanscanprovideadetailedprognosticpredictionforSCLC.

简介：AbstractObjective:Most patients with advanced lung cancer have a poor prognosis. Recent studies have identified TRIM59 as a novel molecule that serves as a prognostic factor for the progression of non-small cell lung cancer. In the present study, we investigated the role of TRIM59 in predicting the prognosis of lung adenocarcinoma (LUAD) as well as the correlation between TRIM59 expression and immune infiltrates.Methods:We analyzed TRIM59 expression in normal and tumor tissues based on RNA-sequencing datasets from The Cancer Genome Atlas and Genotype-Tissue Expression databases. Forty-seven cases of LUAD tissues and their matching adjacent tissues were collected, and TRIM59 expression in tissue samples was demonstrated by immunohistochemistry. All tissue specimens were obtained under the approval of the Medical Ethics Committee of the Second Affiliated Hospital of Zhejiang University School of Medicine (approval No. IR2019001101; approved on April 3, 2019). The immune cell scores were calculated using the CIBERSORT database. The Tumor Immune Estimation Resource database was used to analyze the correlation between TRIM59 and immune cell activities.Results:TRIM59 was up-regulated in most cancer types. High TRIM59 expression predicted a worse prognosis in patients with LUAD (overall survival, P= 0.00096; disease-specific survival, P= 0.00056; disease-free interval, P= 0.0009; progression-free interval, P= 0.0012). Moreover, TRIM59 was highly expressed in patients with LUAD who had a poorer prognosis. TRIM59 also showed a significant correlation with the ESTIMATE score (P = 0.04) and stromal score (P = 0.005) in patients with LUAD. Notably, a significant correlation between TRIM59 and the tumor mutation burden was found in LUAD but in no other cancer types (P < 0.001). Further investigation showed that TRIM59 had a significant correlation with gene markers on neutrophils and dendritic cells.Conclusion:TRIM59 is a potential prognosticator in LUAD and may be correlated with immune cell identification, immune cell infiltration, and immunotherapy checkpoints in LUAD.

简介：Objective:Cancercellradioresistanceisastumblingblockinradiationtherapy.TheactivityinthenuclearfactorkappaB(NFκB)pathwaycorrelateswithanti-apoptoticmechanismsandincreasedradioresistance.TheIKKcomplexplaysamajorroleinNFκBactivationuponnumeroussignals.Inthisstudy,weexaminedtheinteractionbetweenionizingradiation(IR)anddifferentmembersoftheIKK-NFκBpathway,aswellasupstreamactivators,RAF1,ERK,andAKT1.Methods:Theeffectof4GyofIRontheexpressionoftheRAF1-ERK-IKK-NFκBpathwaywasexaminedinA549andH1299lungcancercelllinesusingWesternblotanalysisandconfocalmicroscopy.WeexaminedchangesinradiationsensitivityusinggenesilencingorpharmacologicalinhibitorsofERKandIKKβ.Results:IKKα,IKKγ,andIκBαincreaseduponexposuretoIR,therebyaffectingnuclearlevelsofNFκB(phospho-p65).ERKinhibitionorsiRNA-mediateddown-regulationofRAF1suppressedthepost-irradiationsurvivaloftheexaminedlungcancercelllines.AsimilareffectwasdetectedonsurvivaluponsilencingIKKα/IKKγorinhibitingIKKβ.Conclusions:ExposureoflungcancercellstoIRresultsinNFκBactivationviaIKK.ThegeneticorpharmacologicalblockageoftheRAF1-ERK-IKK-NFκBpathwaysensitizescellstotherapeuticdosesofradiation.Therefore,theIKKpathwayisapromisingtargetfortherapeuticinterventionincombinationwithradiotherapy.

简介：A60-year-oldwomanwithsquamouscellcarcinomaintherightlungwassuccessfullytreatedwithfourcyclesofcombinationchemotherapyaftersurgery,andcompleteremissionwasachieved.However,thepatientdevelopedmyelodysplasticsyndrome(MDS)RAEB-2withmyelofibrosisafterremission,possiblybecauseofchemotherapyorDNAmethylation.Thepatientrespondedwelltodacitabine(Dacogen),suggestingthatDNAhypomethylationagentscanbeapromisingtherapytoretardtheprogressionofasecondtumororcarcinoma.

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简介：Extrapulmonarysmallcellcarcinoma(EPSCC)isarareneoplasmcomprising2.5%to5%ofsmallcellcarcinomas(SCCs).BladderSCCisthemostcommonsiteofgenitourinarytract.PrimaryrenalSCCisextremelyrare.WereportacaseofprimarySCCofthekidneywhichisrarelyreportedintheurinarytractandpresentsanaggressiveclinicalpicture.A59-year-oldfemalevisitedaurologicclinicwithcomplaintofpersistentleftflanksoreness10yearsafterundergoingrenaltransplantation.Abdominalcomputedtomographyshowedaleftrenalpelvistumor.Afterthepatientreceivedleftnephroureterectomywithbladdercuffresection,herpathologyresultsshowedSCC.Aftersurgery,shereceivedadjuvantsystemicchemotherapy,andherrecoveryhasbeenuneventfulasof8months.PrimaryrenalSCCpresentswithanadvancedtumorstageandashortmediansurvivalperiod,thereforeearlyinterventionandclosefollow-uparerecommended.

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简介：Lungcancerrepresentstheleadingcauseofcancerdeathsinhuman.Non-smallcelllungcancer(NSCLC)accountsforabout75%--85%ofalllungcancersandcanbesurgicallyresectedinonly30%--40%ofpatientswithlimiteddisease.[1’21Theremainingpatients,withlocallyadvancedormetasta...

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