简介:ObjectiveTodetectthecellviabilityandtheexpressionsofstemcellsurfacemarkersafterchemotherapeuticdrugtreatment.MethodsWeobservedthecytotoxiceffectsofthreechemotherapeuticagents[epirubicin(Epi),fluorouracil(5-FU)andcyclophosphamide(Cyc)]inthreecelllines,andthecellviabilitiesafterremovedthesechemotherapeuticagents.ExpressionsofstemcellsurfacemarkersCD44,CD24,CD90,CD14andaldehydedehydrogenase1(ALDH1)inbreastcancercellswereanalyzedbyreal-timePCR.Theposthocanalysis(Tukey’stests)inconjunctionwithone-wayANOVAwasusedforstatisticalanalysis.ResultsTheinitialcytotoxicefficacywasmostnotable.Afterthetreatmentofthesametherapeuticagents,cellviabilitywasdecreasedby64.8%35.14%,32.25%inBT-483cells,66.4%,22.94%and45.88%inMDA-MB-231cells,97.1%,99.5%and76.4%inMCFcells.Thedifferencewassignificantcomparedwiththatbeforetreatment(P=0.000).However,theinhibitoryeffectswerediminishedafterchemotherapeuticagentwithdrawal.Cellviabilitieswereincreasedto167.9%,212.04%and188.66%inMDA-MB-231cellsat48hafterwithdrawal.At72hafterwithdrawal,cellviabilitywasincreasedwithasignificantdifferenceinthreecelllines(allPvalues=0.000).ExpressionsofCD44andALDH1weremostprevalentforMDA-MB-231,BT-483andMCF-7cells.ALDH1mRNAlevelwassignificanthigherinBT-483(HER-2overexpressioncellline)thanMDA-MB-231(triplenegativecellline)(P=0.012).CD14mRNAlevelinMCF-7cellsweresignificantlylowerthanthatinMDA-MB-231andBT-483(P=0.003,0.001).BT-483showedsignificantlyhigherlevelofCD44thanMDA-MB-231andMCF-7cellline(P=0.013,0.020),andnosignificantdifferencewasdetectedbetweenMDA-MB-231andMCF-7breastcancercells(P=0.955).CD90mRNAexpressionsweredetectedinMDA-MB-231cellsandMCF-7cells,butnotinBT-483cells.ConclusionSomemalignantcellscouldsurviveinvitroandbegintoproliferateagainbetweencyclesofchemotherapy.
简介:Thecurrentconceptof“AdoptiveTCellImmunotherapyofCancer”isquitedifferentfromhowitwasoriginallyconceived.Withthedevelopmentofmoderntechnologyinmolecularbiology,cellbiology,immunologyandbiochemistryduringthelasttwentyyearsorso,adoptiveimmunotherapyhasgrownfromitsinitialformofasimple“bloodcelltransfer”intoitspresentprocesswhichinvolveshostvauccination,effectorcellactivation/polarizationandgeneticmodification.Withtheuseofimmuneadjuvantsandtheidentification/characterizationoftumor-reactiveTcellsubsets,orincombinationwithothertherapeuticstrategies,adoptivelytransferredTcellshavebecomemuchmorepotentinmediatingtumorregression.Inaddition,studiesonthetraffickingofinfusedTcells,celltransferperformedinlymphopenicmodels,aswellasthediscoveryofnoveltechniquesinimmunemonitoringforthegenerationofeffectorcellsinvitroandaftercelltransferinvivohaveprovidedusefultoolstofurtherimprovethetherapeuticefficacyofthisapproach.ThisarticlewillreviewtheserelatedaspectsofadoptiveTcellimmunotherapyofcancerwithspecificcommentsoncertaincriticalareasintheapplicationofthisapproach.Withtherapidlyevolvingadvancesinthisarea,itishopedthatthiscellularimmunologictherapyasitwasconceptualizedinthepast,canbecomemoreusefulinthetreatmentofhumancancerinthenearfuture.
简介:超声能不仅在检查,而且在治疗被使用,特别在癌症的治疗。Sonodynamic治疗是使用超声提高作为sonosensitizers知道的代理人的细胞毒素的效果的一个试验性的癌症治疗方法。它在vitro并且在vivo被测试了。超声能在一些直接改变房间膜渗透的条件下面渗透织物和房间,从而在某度允许外长的分子的交货进房间。超声能禁止增长或在vitro或在vivo导致癌症房间的apoptosis。低频率的显示的最近的研究和低紧张的超声能导致房间apoptosis,它能被sonodynamic敏感加强,microbubbles,化学疗法的药等等。超声的大多数类型通过导致癌症房间的apoptosis压制了癌症房间的增长。apoptosis的机制不是清楚的。在这评论,我们将集中于并且由超声讨论癌症房间apoptosis的正式就职的机制。
简介:Cancercelldormancyisthemaincauseofcancerrecurrenceandfailureoftherapyasdormantcellsevadenotonlytheanticancerdrugsbutalsothehostimmunesystem.Thesedormantcellsveilthemselvesfromdetectionbyimagingand/orusingbiomarkers,whichimposesanadditionalproblemintargetingsuchcells.Asimilarformofhibernationprocessknownasencystationisstudiedindetailforpathogenicunicellulareukaryoticmicroorganisms.Byexaminationusingmicroarraygeneexpressionprofiles,immunocytochemistrytools,andsiRNAsduringtheprocessofencystation,understandingthecovertfeaturesofcancercelldormancyasproposedcouldbepossible.Thisknowledgecanbeextendedtodormantcancercellstouncoverthemechanismsthatunderliethisghost,yetdangerousstateofhumancancers.Weproposeastrategytoinducedormancyandexitthisstatebyapplicationofknowledgegainedfromtheencystationinductionandretrievalprocessesinpathogeniceukaryoticmicroorganisms.Giventhatearlydetectionandcharacterizationofdormantmalignanttumorcellsisimportantasageneralstrategytomonitorandpreventthedevelopmentofovertmetastaticdisease,thishomologymayenablethedesignoftherapiesthatcouldeitherawakethedormantcellfromdormancytomakeitavailablefortherapiesorprolongsuchaphasetomakecancerappearasachronicdisease
简介:AbstractBackground:Previous studies have shown that bufalin exerts antitumor effects through various mechanisms. This study aimed to determine the antineoplastic mechanism of bufalin, an extract of traditional Chinese medicine toad venom, in ovarian cancer.Methods:The 3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl tetrazolium bromide (MTT), 5-ethynyl-2′-deoxyuridine (EdU), and colony formation assays were used to investigate the antiproliferative effect of bufalin on the ovarian cancer cell line SK-OV-3. Molecular docking was used to investigate the combination of bufalin and epidermal growth factor receptor (EGFR) protein. Western blotting was performed to detect the expression of EGFR protein and its downstream targets.Results:Bufalin inhibited the proliferation of SK-OV-3 cells in a dose- and time-dependent manner. Bufalin was confirmed to combine with EGFR protein using molecular docking and downregulate expression of EGFR. Bufalin inhibited phosphorylation of EGFR, protein kinase B (AKT), and extracellular signal-regulated kinase (ERK).Conclusion:Bufalin suppresses the proliferation of ovarian cancer cells through the EGFR/AKT/ERK signaling pathway.
简介:
简介:MicroRNAs(miRNAs)内长的、小、非编码的RNA,它能够在post-transcriptional的silencing基因表示铺平。在这研究,我们报导miR-205是显著地在与匹配的正常的胸织物相比的胸肿瘤的underexpressed。同样,包括MCF-7和MDA-MB-231,乳癌房间行比非恶意的MCF-10A房间表示低级miR-205。兴趣,miR-205的宫外的表示显著地禁止房间增长和抛锚独立人士生长,以及房间侵略。而且,miR-205被显示在一个动物模型压制肺转移。最后,西方的污点与试金表明的酶记者结合了那ErbB3和脉管的endothelial生长因素A(VEGF--一)是为miR-205的直接目标,并且这miR-205-mediated抑制通过和在ErbB3和VEGF的3鈥?untranslated区域(3鈥?UTR)的通常认为的miR-205绑定地点的直接相互作用是可能的--一。一起,这些结果建议miR-205是在乳癌的肿瘤suppressor。
简介:Smoothened(SMO)是表明小径的刺猬的一个重要成员。我们为RNA干扰构造了特定的recombinantlentiviral向量,指向SMO基因(NM_005631)观察它在人的雄激素敏感的前列腺癌症房间线的SMO表示,房间增长和房间周期上的效果,LNCaP,并且在雄激素无关的前列腺癌症房间线,PC3。四个siRNA序列被设计并且插入了到lentiviral向量pGCSIL-GFP构造四recombinant向量。有最高的介入效率的向量是有在293T房间包装向量(pHelper1.0和pHelper2.0)为分别地感染LNCaP和PC3房间线由liposome装配lentivirus粒子的co-transfected。SMOmRNA,肿瘤房间增长和房间周期的表示水平被量的实时聚合酶链反应(qRT-PCR)测量,3-(4,5)-dimethylthiahiazo(-z-y1)-3,5-di-phenytetrazoliumromide(MTT)试金和流动cytometry分别地。顺序结果证明recombinantlentiviral向量成功地被构造。pGCSIL-GFP-723有最高的介入效率,在co-transfection,LNCaP和PC3房间与排队以后的命名Lv-SIL-SMO723被感染。与控制组相比,显著地显示出的结果减少了(P<0.05)LNCaP和PC3,S阶段房间的更低的吝啬的百分比和G2/M的更高吝啬的百分比的SMOmRNA表情分阶段执行房间,以及显然减缓增长(P<0.01)在感染的组的LNCaP。然而,PC3的增长没被改变(P>0.05)。在结论,recombinantlentivirus粒子能压制SMO表示,在LNCaP和PC3房间线调整房间周期并且显著地禁止LNCaP房间然而并非PC3房间的增长。
简介:AbstractImmunotherapy has dramatically altered the treatment of non-small cell lung cancer. Currently, the emergence of combination strategies in immunotherapy has brightened the prospects of improved clinical outcomes and manageable safety profiles in the first/second-line settings. However, sub-optimal response rates are still observed in several clinical trials. Hence, alternative combination models and candidate selection strategies need to be explored. Herein, we have critically reviewed and commented on the published data from several clinical trials, including combined immunotherapy and chemotherapy, anti-angiogenic agents, epidermal growth factor receptor/anaplastic lymphoma kinase tyrosine kinase inhibitors, radiotherapy, and other immune checkpoint inhibitors.
简介:尽管非小的细胞肺癌症(NSCLC)能转移到几乎任何东西器官,到有重要临床的表明的胆囊的转移是相对稀罕的。这里,我们报导作为尖锐胆汁介绍的NSCLC的胆囊转移的一个案例。在恰好上面的象限和发烧疼痛地介绍的一个79岁的人。胸和腹部的计算断层摄影术(CT)扫描在胆囊变厚的肺和不规则的墙的恰好更低的脑叶显示出一个cavitary团。肺团的开的胆囊炎和针活体检视被执行。胆囊的组织学的检查揭示了显示象针活体检视估计的肺团的一样的形态学的中等区分的有鳞的房间癌。胆囊和肺织物的随后的immunohistochemical检查证明肿瘤房间为P63是积极的但是为cytokeratin否定7,cytokeratin20并且甲状腺抄写factor-1。胆囊的第二个主要肿瘤被immunohistochemical方法排除,并且最后的病理学的诊断是NSCLC的胆囊转移。尽管发生是极其稀罕的,尖锐胆汁能与肺癌症转移联合发生到胆囊。
简介:(PGAM1)Phosphoglycerate变位酶1是在许多癌症类型的upregulated并且在房间增长,移植,侵略,和apoptosis包含。然而,在PGAM1和前列腺癌症之间的关系糟糕被理解。现在的学习与正常前列腺纸巾相比在前列腺癌症纸巾在PGAM1表示调查了变化并且检验了有clinicopathological变量的PGAM1和它的关系的细胞的函数。Immunohistochemistry并且西方的弄污表明那PGAM1表情是在前列腺癌症纸巾和房间线的upregulated。PGAM1表示与格利森分数被联系(P=0.01)并且T阶段(P=0.009)。由在PC-3和22Rv1前列腺癌症房间线的siRNA的PGAM1击倒禁止的房间增长,移植,和侵略和提高的癌症房间apoptosis。在一个裸体老鼠异种皮移植模特儿,PGAM1击倒的显著地压制的肿瘤生长。PGAM1的删除导致了MMP-2的Bcl-2,Bax的提高的表示,caspases-3和抑制的减少的表示和MMP-9表示。我们的结果显示PGAM1可以在前列腺癌症前进和攻击性起一个重要作用,并且它可能为前列腺癌症是差的预后和一个潜在的治疗学的目标的一个珍贵标记。
简介:Objective:Chemotherapyisthestandardtreatmentforsmall-celllungcancer(SCLC),andleukopeniaisacommonsideeffect.Thisstudyassesseswhetherchemotherapy-inducedleukopeniaisapredictorofefficacyandwhetheritisassociatedwiththesurvivalofSCLCpatients.Methods:Aretrospectiveanalysiswasconductedondatafrom445patientswithSCLCwhoreceivedstandardchemotherapyfor4to10cycles.TheWorldHealthOrganizationgradingsystemclassifiesleukopeniaduringchemotherapyasfollows:absent(grade0),mild(grades1and2),orsevere(grades3and4).Theprimaryendpointisoverallsurvival(OS).Results:Theassociationbetweenchemotherapy-inducedleukopeniaandOSwasassessed.AccordingtoamultivariateCoxmodelwithtime-varyingcovariates,thehazardratioofdeathwassignificantlyloweramongpatientswithmildleukopeniathanamongpatientswithsevereleukopeniaat0.687(0.506to0.943)and1.414(1.147to1.744),respectively.Themediansurvivalwas13months(95%CI:11to15months)forpatientswhodidnotexperienceleukopenia,17months(95%CI:14to18months)forthosewithmildleukopenia,and14months(95%CI:13to16months)forthosewithsevereleukopenia(absentvs.mildvs.severeleukopenia,P=0.047).Conclusion:LeukopeniaduringchemotherapyisassociatedwiththesurvivalofSCLCpatients.Mildleukopeniaisstronglyassociatedwithlongersurvivaltime.
简介:Objective:ToevaluatedBromodeoxyuridine(BrdUrd)/DNAdoubleparametricmethodindetectionofgastriccarcinomaandtoanalyzetherelationshipsofcellularBrdUrdlabelingindices(LI),G2/M-phasefraction(G2/MPE)andDNAcontenttothedepthofinvasion,lymphaticvesselinvasion,lymphaticnodemetastasis,peritonealdisseminationandbloodvesselinvasionandprognosis.Methods:Freshtumorsamplesfrom60caseswereexaminedbyBrdUrd/DNAdoubleparametricflowcytometry.Propidiumiodide(PI)wasusedasfluorescentprobefortotalcellularDNAandamonoclonalantibodyagainstBrdUrdincorporatedintoDNA.Fluorescein-labeledgoatanti-mouseantibodywasusedassecondantibody.Results:ThevaluesofBrdUrdLIinpatientswithserosainvasionwassignificantlyhigherthanthosewithoutserosainvasion(P<0.01);therewasstatisticalsignificancein5-yearsurvivalratebetweenthetwogroups(P<0.01).BothBrdUrdLIandG2/MPFvaluesweresignificantlyhigherinpatientswithlymphaticvesselinvasionthanthosewithoutinvasion(P<0.01);thepatientswithlymphaticvascularinvasioncarriedasignificantlypoorprognosis(P<0.01).BothBrdUrdLIandG2/MPFvaluesweresignificantlyhigherinpatientswithlymphaticnodemetastasisthanthosewithoutmetastasis(P<0.01),therewasastatisticalsignificancein5yearssurvivalbetweenthese2groups.Theincidenceoflymphaticnodemetastasiswassignificantlyhigherinaneuploidcarcinoma(P<0.05),andthepatientswithaneuploidcarriedasignificantlypoorprognosis(P<0.05).Patientswithperitonealdisseminationhadasignificantlyworseprognosis(P<0.01).G2/MPFvaluesweresignificantlyhigherinpatientswithbloodvesselinvasionthanthosewithoutinvasion(P<0.01).Conclusion:CellularBrdUrdLI,G2/MPFandDNAcontentarerelatedtodepthofinvasion,lymphaticvesselinvasion,peritonealdissemination,bloodvesselinvasionandprognosisofgastriccarcinoma.
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.
简介:AbstractHistorically, breast cancer has been regarded as an immunogenic "cold" tumor. However, the discovery of immune checkpoint inhibitors has made immunotherapy becoming an emerging new treatment modality for breast cancer. This review discusses the immune system, immune features of breast cancer, and the programmed cell death protein-1/programmed cell death protein ligand-1 (PD-1/PD-L1) inhibitors used in the treatment of breast cancer. High T lymphocyte infiltration and mutation burden were observed in triple-negative breast cancer and human epidermal growth factor receptor 2 positive breast cancer. Increasing breast cancer immunogenicity and modulating the tumor microenvironment has been reported to improve the therapeutic efficacy of immunotherapy. Recent clinical trials involving PD-1/PD-L1 inhibitors monotherapy in breast cancer has revealed little efficacy, which highlights the need to develop combinations of PD-1/PD-L1 inhibitors with chemotherapy, molecularly targeted therapies, and other immunotherapies to maximize the clinical efficacy. Collectively, the immunotherapy might be a promising therapeutic strategy for breast cancer and several clinical trials are still on-going.
简介:AbstractObjective:The majority of non-small cell lung cancer (NSCLC) cases remain undiagnosed until advanced stages of the disease. Accumulating studies have highlighted the utility of palliative care as an effective treatment option, which relieves patients’ suffering by activating placebo effect in the body. To evaluate the clinical significance of palliative care, data from NSCLC drug-randomized controlled trials (RCTs) were collected and the effects of placebo treatment examined.Methods:PubMed (MEDLINE), Scopus, Web of Science, and China National Knowledge Infrastructure databases were searched from January 1,1978 to September 1,2020. Placebo-controlled phase II/III pharmaceutical RCTs enrolling patients with solely stage III/IV NSCLC were included. The quality of included studies was assessed using the Jadad method. Single-arm and two-arm meta-analyses of the therapeutic and adverse effects of placebo, that is, the primary and secondary outcome measures, were subsequently performed using either Bayesian or conventional models.Results:Five RCTs including 2245 drug-treated and 1510 placebo-treated patients at NSCLC stage III or IV were included for the study. Low risk of bias was observed for all five included studies using the Cochrane method. Following placebo treatment, controlled disease rate of 24.1% (95% credible interval [CrI], -0.126-0.609) and dropout rate of 2.1% (95% CrI, 0.007-0.039) were calculated, with a dose reduction rate of 3.0% (95% CrI, 0.017-0.045). Compared with active drug treatment, the placebo treatment group had a risk ratio of 0.81 (95% confidence interval, 0.68-0.97) and 0.85 (95% confidence interval, 0.76-0.96) for the achievement of progression-free survival and overall survival, respectively.Conclusion:In NSCLC drug RCTs, placebo treatment is indicated to generally induce low toxicity in patients by dropout and dose reduction rates and adverse events, although the therapeutic responses could not be precisely determined. The results suggest that under specific circumstances, palliative care which can activate placebo effect may have similar effects as active drugs (such as erlotinib, vandetanib, or pemetrexed) in terms of prolonging survival time.