简介：Objective:Toinvestigatethesignificanceofextra-nodalspreadinspecialhistologicalsub-typesofbreastcancerandtherelationshipofsuchspreadwithprognosticparameters.Methods:Atotalof303breastcancercaseswereclassifiedaccordingtotumortype,andeachtumorgroupwassubdividedaccordingtoage,tumordiameter,lymphnodemetastasis,extra-nodalspread,veininvasionintheadjacentsofttissue,distantmetastasis,andimmunohistochemicalcharacteristics[estrogenreceptor(ER),progesteronereceptor(PR)existence,p53,c-erbB-2,andproliferativerate(Ki-67)].The122caseswithextra-nodalspreadwereclinicallyfollowedup.Results:Anextra-nodalspreadwasobservedin40%(122cases)ofthe303breastcancercases.Thespreadmostfrequentlypresentedinmicropapillarycarcinomahistologicalsub-type(40cases,75%),butleastfrequentlypresentsinmucinouscarcinoma(2cases,8%).Patientswithextra-nodalspreadhadahighaveragenumberofmetastaticlymphnodes(8.3)andahighdistantmetastasisrate(38cases,31%)comparedwithpatientswithoutextra-nodalspread.Conclusion:Theexistenceofextra-nodalspreadintheexaminedbreastcancersub-typeshaspredictivevalueinforecastingthenumberofmetastaticlymphnodesandthediseaseprognosis.

简介：客观：为了学习表达式和apoptosis的临床的价值，在乳癌控制基因bcl-2和bax。方法：在在1996在我们的医院里从操作获得的41乳癌的蛋白质bax和bcl-2与正常的胸纸巾用ABCimmunohistochemical污点试金并且与10个盒子相比被检测。结果：在正常的胸组织的bax的积极的率是90%并且在乳癌是59%，与他们之间的重要统计差别(P<0.05)，但是在bcl-2没有统计差别蛋白质表示。在41乳癌之中，有淋巴节点转移(21个盒子)的组有显然低的bax表示(43%)和高bcl-2表示(76%)，给没有淋巴节点转移的组显示出重要差别(P<0.05)。结论：bcl-2的antiapoptosis功能是比在乳癌的bax强壮的。蛋白质bax和bcl-2试金可能在理解乳癌的生物行为是有用的。

简介：肿瘤坏死因素(TNF)联系了导致apoptosisligand(TRAIL/APO2L)是在血缘的死亡受体的约会之上导致apoptosis的TNF基因总科的一个成员。当小道对正常房间相对无毒时，它有选择地在许多转变房间导致apoptosis。不过，胸肿瘤房间对小道的效果特别地抵抗。这里，我们报导在有cyclin依赖的kinase禁止者roscovitine的联合，落后于的暴露在检验的小道抵抗的乳癌房间线的多数导致了显著apoptosis。Roscovitine便于小道导致死亡的发信号的复杂形成和caspase-8的激活。FLICE禁止的蛋白质是的cFLIP(L)和cFLIP显著地下面调整的列在后面暴露到roscovitine并且，确实由siRNA的cFLIPisoforms击倒敏化的胸肿瘤房间到导致小道的apoptosis。另外，我们证明roscovitine强烈在胸肿瘤房间压制了Mcl-1表示和起来调整的E2F1蛋白质层次。显著地，由siRNA的Mcl-1的silencing敏化胸肿瘤房间到导致小道的apoptosis。而且，由减少的siRNA的E2F1蛋白质击倒在导致小道的apoptosis的roscovitine的敏化的效果。在摘要，我们的结果为roscovitine的pro-apoptotic影响揭示pleitropic机制，加亮它象在在有小道的联合的乳癌的一个反肿瘤代理人的潜力。

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简介：Objective:Toidentifydifferentiallyexpressedlongnon-codingRNAs(lncRNAs)involvedinthemetastasisofepithelialovariancancer.Methods:AninvitroinvasionassaywasperformedtovalidatetheinvasivecapabilityofSKOV3andSKOV3.ip1celllines.TotalRNAwasthenextracted,andmicroarrayanalysiswasperformed.Moreover,ninelncRNAswereselectedforvalidationusingRT-qPCR.Results:ComparedwiththeSKOV3cells,theSKOV3.ip1cellssignificantlyimprovedintheinvitroinvasiveactivity.Ofthe4,956lncRNAsdetectedinthemicroarray,583and578lncRNAswereupregulatedanddownregulated,respectively,inSKOV3.ip1cells,comparedwiththeparentalSKOV3cells.SevenoftheanalyzedlncRNAs(MALAT1,H19,UCA1,CCAT1,LOC645249,LOC100128881,andLOC100292680)confirmedthederegulationfoundbymicroarrayanalysis.Conclusion:LncRNAsclustersweredifferentiallyexpressedinovariancancercellswithvaryingmetastaticpotentials.ThisresultindicatesthatsomelncRNAsmightexertapartialorkeyroleinepithelialovariancancermetastasis.FurtherstudiesshouldbeconductedtodeterminetherolesoftheselncRNAsinovariancancermetastasis.

简介：AbstractBackground:Breast cancer patients with ipsilateral supraclavicular lymph node metastasis (ISLNM) but without distant metastasis are considered to have a poor prognosis. This study aimed to develop a nomogram to predict the overall survival (OS) of breast cancer patients with ISLNM but without distant metastasis.Methods:Medical records of breast cancer patients who received surgical treatment at the Affiliated Cancer Hospital of Zhengzhou University, Jiyuan People’s Hospital and Huaxian People’s Hospital between December 21, 2012 and June 30, 2020 were reviewed retrospectively. Overall, 345 patients with pathologically confirmed ISLNM and without evidence of distant metastasis were identified. They were further randomized 2:1 and divided into training (n = 231) and validation (n = 114) cohorts. A nomogram to predict the probability of OS was constructed based on clinicopathologic variables identified by the univariable and multivariable analyses. The predictive accuracy and discriminative ability were measured by calibration plots, concordance index (C-index), and risk group stratification.Results:Univariable analysis showed that estrogen receptor-positive (ER+), progesterone receptor-positive (PR+), human epidermal growth factor receptor 2-positive (HER2+) with Herceptin treatment, and a low axillary lymph node ratio (ALNR) were prognostic factors for better OS. PR+, HER2+ with Herceptin treatment, and a low ALNR remained independent prognostic factors for better OS on multivariable analysis. These variables were incorporated into a nomogram to predict the 1-, 3-, and 5-year OS of breast cancer patients with ISLNM. The C-indexes of the nomogram were 0.737 (95% confidence interval [CI]: 0.660-0.813) and 0.759 (95% CI: 0.636-0.881) for the training and the validation cohorts, respectively. The calibration plots presented excellent agreement between the nomogram prediction and actual observation for 3 and 5 years, but not 1 year, OS in both the cohorts. The nomogram was also able to stratify patients into different risk groups.Conclusions:In this study, we established and validated a novel nomogram for predicting survival of patients with ISLNM. This nomogram may, to some extent, allow clinicians to more accurately estimate prognosis and to make personalized therapeutic decisions for individual patients with ISLNM.

简介：AbstractBackground:Ubiquitin-conjugating enzyme E2C (UBE2C) has been shown to be associated with the occurrence of various cancers and involved in many tumorigenic processes. This study aimed to investigate the specific molecular mechanism through which UBE2C affects breast cancer (BC) proliferation.Methods:BC-related datasets were screened according to filter criteria in the Gene Expression Omnibus (GEO) database and The Cancer Genome Atlas (TCGA) database. Then differentially expressed genes (DEGs) were identified using Venn diagram analysis. By using DEGs, we conducted the following analyses including Gene ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG), protein-protein interaction (PPI), and survival analysis, and then validated the function of the hub gene UBE2C using quantitative reverse transcription-polymerase chain reaction (RT-qPCR), cell counting kit-8 (CCK-8) assay, transwell assay, and Western blot assay.Results:In total, 151 DEGs were identified from the GEO and TCGA databases. The results of GO analysis demonstrated that the DEGs were significantly enriched with mitotic nuclear division, lipid droplet, and organic acid-binding. KEGG analysis showed that the peroxisome proliferators-activated receptor (PPAR) signaling pathway, regulation of lipolysis in adipocytes, and proximal tubule bicarbonate reclamation were significantly enriched in the signal transduction pathway category. The top three hub genes that resulted from the PPI network were FOXM1, UBE2C, and CDKN3. The results of survival analysis showed a close relationship between UBE2C and BC. The results of CCK-8 and transwell assays suggested that the proliferation and invasion of UBE2C knockdown cells were significantly inhibited (P < 0.050). The results of Western blot assay showed that the level of phosphorylated phosphatase and tensin homology deleted on chromosome 10 (p-PTEN) was obviously increased (P < 0.050), whereas the levels of phosphorylated protein kinase B (p-AKT), phosphorylated mammalian target of rapamycin (p-mTOR), and hypoxia-inducible factor-1 alpha (HIF-1α) were dramatically decreased (P < 0.050) in the UBE2C knockdown cell.Conclusion:UBE2C can promote BC proliferation by activating the AKT/mTOR signaling pathway.

简介：AbstractBackground:Recent studies identifying methylenetetrahydrofolate reductase (MTHFR) polymorphisms associated with breast cancer (BC), ovarian cancer (OC), cervical cancer, and endometrial cancer (EC) have reported conflicting results and been underpowered. To clarify the correlation between MTHFR mutations and these common female malignancies, we conducted a comprehensive meta-analysis incorporating all eligible publications.Methods:Relevant reports published before January 20, 2020, were retrieved from PubMed, Embase, the Cochrane Library, and the China National Knowledge Infrastructure databases. The odds ratio and 95% confidence interval summaries for the MTHFR 677C/T and 1298A/C polymorphisms in BC, OC, cervical cancer, and EC were estimated.Results:A total of 171 studies comprising 56,675 cancer cases and 67,559 controls were included. The results showed a markedly elevated risk of cancer susceptibility related to MTHFR 677C/T based on all genetic models. Similarly, we identified a significant correlation between 1298A/C mutation and cancer risk based on overall comparisons among all models, except the heterozygous model. Moreover, subgroup analysis by cancer type revealed a significantly increased risk of BC associated with 677C/T in the five models and of cervical cancer associated with 1298A/C in some models. Based on ethnicity, significant associations were observed between Asian, African, and mixed populations for 677C/T and the Asian population for 1298A/C. With regard to the sample type used for analysis, we detected a positive association between using blood as the DNA source and cancer risk for 677C/T in all genetic models and for 1298A/C in some genetic models. Further stratification of the results revealed that a notably increased risk was associated with the use of polymerase chain reaction-restriction fragment-length polymorphism or TaqMan as the genotyping method, as well as with the use of population-or hospital-based groups as the controls for 677C/T and 1298A/C, respectively.Conclusion:This meta-analysis suggests that MTHFR 677C/T and 1298A/C polymorphisms correlate with the risk of common gynecological cancers, with these findings potentially applicable for overall comparisons of related data.

简介：Objective:MicroRNA-21(miR-21)hasbeenshowntobeakeyregulatorofcarcinogenesis.TherewerefewreportsaboutthecomparisonofserummiR-21withconventionaltumormarkers.ThisstudyaimedtoexplorethediagnosticvalueofcirculatingmiR-21asatumormarkerinbreastcancer(BC)andcompareitwithCA153andcarcinoembryonicantigen(CEA).Methods:CirculatingmiR-16andmiR-21wereamplifiedandquantitativelydetectedbyreal-timePCRin89BCpatientsand55healthycontrols.ThelevelsofCA153andCEAweremeasuredthroughelectrochemiluminescenceassays.ThenthesensitivityindiagnosisofBCwascomparedamongmiR-21,CA153andCEA.Results:ThelevelofserummiR-21wassignificantlyhigherinBCpatientsthancontrols(P<0.001).ThesensitivityandspecificityofmiR-21were87.6%and87.3%,respectively,whereasthesensitivitiesofCEAandCA153wereonly22.47%and15.73%.Conclusions:ComparedwithCEAandCA153,serummiR-21hasahighersensitivityindiagnosisofBC.AlthoughnotcorrelatedwiththestatusofER,PRandclinicalstages,serummiR-21maybeapotentialdiagnosticindicatorforBC,especiallyfortheearlystage.

简介：AbstractBackground:Methylene blue is the most commonly used tracer for sentinel lymph node (SLN) biopsy (SLNB) in China. This study aimed to investigate the feasibility of clinical application of SLNB using methylene blue dye (MBD) for early breast cancer and the prognosis of patients with different SLN and non-SLN statuses.Methods:We retrospectively analyzed the clinicopathological data of patients with early breast cancer treated at the Peking University First Hospital between 2013 and 2018. We calculated the SLN identification rate (IR) in SLNB with MBD and the false-negative rate (FNR), and analyzed the prognosis of patients with different SLN and non-SLN statuses using Kaplan-Meier curves.Results:Between January 2013 and December 2018, 1603 patients with early breast cancer underwent SLNB with MBD. The SLN IR was 95.8% (1536/1603). Two SLNs (median) were detected per patient. There were significant differences in FNR between patients with SLN micrometastasis and macrometastasis (19.0% vs. 4.5%, χ2 = 12.771, P < 0.001). Chi-square test showed that there were significant differences in SLN successful detection rates among patients with different vascular tumor embolism status (96.3% vs. 90.8%, χ2 = 9.013, P = 0.003) and tumor (T) stages (96.6% vs. 94.1%, χ2 = 5.189, P = 0.023). Multivariate analysis showed that vascular tumor embolism was the only independent factor for SLN successful detection (odds ratio: 0.440, 95% confidence interval: 0.224-0.862, P = 0.017). Survival analysis showed a significant difference in disease-free survival (DFS) between patients with non-SLN metastasis and patients without non-SLN metastasis (P = 0.006).Conclusion:Our single-center data show that, as a commonly used tracer in SLNB in China, MBD has an acceptable SLN IR and a low FNR in frozen sections. This finding is consistent with reports of dual tracer-guided SLNB. Positive SLNs with non-SLN metastasis are associated with DFS.

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简介：Objective:Avarietyofionchannelshavebeenimplicatedinbreastcancerproliferationandmetastasis.VoltagegatedK+(Kv)channelsnotonlycauserepolarizationinexcitablecells,butarealsoinvolvedinmultiplecellularfunctionsinnon-excitablecells.InthisstudyweinvestigatedtheroleofKvchannelsinmigrationofBT474breastcancercells.Methods:Transwelltechniquewasusedtoseparatemigratorycellsfromnon-migratoryonesandthesetwogroupsofcellsweresubjecttoelectrophysiologicalexaminationsandmicrofluorimetricmeasurementsforcytosolicCa2+.CellmigrationwasexaminedintheabsenceorpresenceofKvchannelblockers.Results:Whencomparedwithnon-migratorycells,migratorycellshadmuchhigherKvcurrentdensities,butratherunexpectedly,moredepolarizedmembranepotentialandreducedCa2+influx.Reversetranscriptasepolymerasechainreaction(RT-PCR)analysisrevealedthepresenceofKv1.1,Kv1.3,Kv1.5,Kv2.1,Kv3.3,Kv3.4andKv4.3channels.Cellmigrationwasmarkedlyinhibitedbytetraethylammonium(TEA),adelayedrectifierKvchannelblocker,butnotby4-aminopyridine,anA-typeKvchannelblocker.Conclusions:Takentogether,ourresultsshowthatincreasedKvchannelexpressionplayedaroleinBT474cellmigration,andKvchannelscouldbeconsideredasbiomarkersorpotentialtherapeutictargetsforbreastcancermetastasis.Themechanism(s)bywhichKvchannelsenhancedmigrationappearedunrelatedtomembranehyperpolarizationandCa2+influx.

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简介：象为变形阉割抵抗的前列腺癌症(CRPC)的docetaxel和cabazitaxel治疗一样的新奇神经质的治疗的可获得性在没有前进的幸存和全面幸存与改进为这组病人改变了眼界。医生们经常用浆液诊断前列腺癌症的前进前列腺特定的抗原(PSA)。然而，浆液PSA总是没在CRPC与临床的地位被相关。与更大的精确评估PSA动力学，PSA并且CRPC的开发的机制的控制的理解被需要。而且，与最佳地改进预后和病人的QOL的适当预定使用新神经质的治疗是必要的。在现在的评论，我们查明PSA动力学和CRPC的发展的机制为mCRPC在新治疗的最佳的利用帮助。

简介：AbstractBackground:Female breast cancer (FBC) has become the most prevalent malignancy worldwide. We aimed to evaluate the global and regional burden in epidemiological trends and factors associated with the incidence and mortality of FBC.Methods:FBC incidence and mortality in 60 selected countries by cancer registry data integrity in 2020 were estimated from the GLOBOCAN database, and their association with the human development index (HDI) was further evaluated. Trends of age-standardized rates of incidence and mortality in 60 countries from 2000 through 2019 were evaluated by joinpoint regression analysis using data of Global Burden of Disease 2019. The association between potential behavioral, metabolic, and socioeconomic risk factor exposure at the nation level retrieved from the World Bank and Global Health Observatory and the incidence and mortality of FBC were evaluated by multivariate linear regression.Results:FBC incidence and mortality varied greatly in the 60 included countries. Higher incidence and mortality rates were typically observed in countries with higher HDIs and vice versa. During 2000 to 2019, significantly increasing trends in incidence and mortality were observed in 26 (average annual percent changes [AAPCs], 0.35-2.96) and nine countries (AAPC, 0.30-1.65), respectively, while significantly decreasing trends in both incidence and mortality were observed in 22 countries, most of which were high-HDI countries. Among the population aged ≥40 years, there were 26 and 11 countries showing significantly increased trends in incidence and mortality, respectively. Ecological analysis showed that countries with higher prevalence rates of high cholesterol and higher health expenditures were more likely to have higher FBC incidence, and countries with higher rates of obesity and poorer universal health coverage were more likely to have higher FBC mortality.Conclusions:Despite decreased or stabilized FBC incidence and mortality rates were observed in some countries with high HDI over the past decades, disease burden became even severer in developing countries, especially for the population aged ≥40 years. Effective targeted preventive programs are strongly encouraged to reduce the FBC disease burden worldwide.

简介：Objective:Tostudytherelationshipbetweencyclooxygenase-2(COX-2)expressionandtumorangiogenesisinhumanbreastcancer.Methods:Archivalprimarybreastcarcinomas(n=62),adjacentductalcarcinomainsitu(DCIS,n=13)andDCISalone(n=5)wereanalyzedforCOX-2andVEGFexpressionbyimmunohistochemistryusingspecificmonoclonalantibodies.Microvesseldensity(MVD)wasalsoexaminedtheusingCD34staining.Results:AsignificantcorrelationwasfoundbetweenCOX-2andVEGFexpression(P<0.01).BothCOX-2andVEGFweresignificantlycorrelatedwithMVD(P<0.05)andP<0.01,respectively).COX-2andVEGFgeneswereoverexpressedintumorspecimensascomparedwithnormalepithelia.Conclusion:COX-2isrelatedtotumorangiogenesisinbreastcancer.ItislikelythatVEGFisoneofthemostimportantmediatorsoftheCOX-2angiogenicpathway.

简介：Objective:ToinvestigatetheantitumoractivityandthemechanismofBRM-SJSonbreastcancercells.Methods:Flowcytometry,DNAagarosegelelectrophoresisandothertechniqueswereusedtostudytheinvitroandinvivoinhibitoryeffectonBcaP-37cellsbyBRM-SJS.Results:BRM-SJSshowedaninhibitoryrateof33.8%oninvivotransplantedtumor(P<0.05,comparedwithcontrol).TheflowcytometryanalysisofBRM-SJStreatedBcaP-37(2.5μmol/L,5μmol/L,10μmol/Lfor48hand72h)revealedtypicalsub-G1peak.ThespecificDNALadderswereexhibitedwithBRM-SJSBcaP-37cellstreated.Conclusion:BRM-SJShasmarkedantitumoractivityonBcaP-37anditsinhibitoryeffectsontumorwererealizedbybothinductionofapoptosisandnecrosisofthetumorcells.

简介：Intrinsicapoptosis,apossibleresponsetomitochondrialdamage,inMDA-MB-231cellsexposedtodifferentdosesofcarbonionswasinvestigatedinthisstudy.WeassessedBaxandBcl-2expressionandcytochromecreleaseinthemitochondriaandcytosolofcellsexposedtolow(0.5Gy)andhigh(3Gy)dosesofcarbonionsusingwesternblotanalysis.

简介：Objective:Toexploretheeffectsofpostmastectomyradiotherapy(PMRT)onthelocoregionalfailure-freesurvival(LRFFS)andoverallsurvival(OS)ofbreastcancerpatientsunderdifferenttumorstagesandwithonetothreepositiveaxillarylymphnodes(ALNs).Methods:Weconductedaretrospectivereviewof527patientswithonetothreepositivelymphnodeswhounderwentmodifiedradicalorpartialmastectomyandaxillarydissectionfromJanuary2000toDecember2002.ThepatientsweredividedintotheT1-T2N1andT3-T4N1groups.TheeffectsofPMRTontheLRFFSandOSofthesetwopatientgroupswereanalyzedusingSPSS19.0,Pearson’sχ2-test,Kaplan-Meiermethod,andCoxproportionalhazardmodel.Results:ForT1-T2N1patients,nostatisticalsignificancewasobservedintheeffectsofPMRTonLRFFS[hazardratio(HR)=0.726;95%confidenceinterval(CI):0.233-2.265;P=0.582]andOS(HR=0.914;95%CI:0.478-1.745;P=0.784)ofthegeneralpatients.Extracapsularextension(ECE)andhighhistologicalgradeweretheriskfactorsforLRFFSandOSwithstatisticalsignificanceinmultivariateanalysis.StratificationanalysisshowedthatPMRTstatisticallyimprovedtheclinicaloutcomesinhigh-riskpatients[ECE(+),LRFFS:P=0.026,OS:P=0.007;histologicalgradeIII,LRFFS:P<0.001,OS:P=0.007]butnotinlow-riskpatients[ECE(–),LRFFS:P=0.987,OS:P=0.502;histologicalgradeI-II,LRFFS:P=0.816,OS:P=0.296].ForT3-T4N1patients,PMRTeffectivelyimprovedthelocalcontrol(HR=0.089;95%CI:0.210-0.378;P=0.001)ofthegeneralpatients,whereasnostatisticaleffectwasobservedonOS(HR=1.251;95%CI:0.597-2.622;P=0.552).Absenceofestrogenreceptorsandprogesteronereceptors(ER/PR)(–)wasanindependentriskfactor.FurtherstratificationanalysisindicatedastatisticaldifferenceinLRFFSandOSbetweenthehigh-riskpatientswithER/PR(–)receivingPMRTandnotreceivingPMRT[ER/PR(–),LRFFS:P=0.046,OS:P=0.039].However,PMRThadabeneficialeffectonthereductionoflocoregionalr

简介：在乳癌房间在Notch-1小径上调查trastuzumab的效果和机制的目的，认出在trastuzumab抵抗表明小径的Notch-1的意义。