简介：Objective:ToinvestigatetheeffectsofE7080andN5-(1-iminoethyl)-L-ornithinedihydrochloride(L-NIO)oncolorectalcanceraloneandincombination.Methods:HT29colorectalcancercelllinefromSapInstitutewasused.Real-timecellanalysis(xCELLigencesystem)wasperformedtodeterminetheeffectsofE7080andL-NIOoncolorectalcellproliferation.WhileapoptosiswasdeterminedwithAnnexinVstaining,andtheeffectofagentsonangiogenesiswasdeterminedwithchorioallantoicmembrane(CAM)model.Results:WefoundthatE7080hasastrongantiproliferativeeffectwithanhalfmaximuminhibitionofconcentration(IC50)valueof5.60×10–8mol/L.AlsoithasbeenobservedthatE7080showedantiangiogenicandapoptoticeffectsonHT29colorectalcancercells.AntiangiogenicscoresofE7080were1.2,1.0and0.6for100,10and1nmol/LE7080concentrations,respectively.Furthermore,apoptosishasbeendetectedin71%ofHT29colorectalcancercellsafteradministrationof100nmol/LE7080whichmayindicatestrongapoptoticeffect.MeanwhileadministrationofL-NIOalonedidnotshowanyeffect,butthecombinationofE7080withL-NIOincreasedtheantiproliferative,antiangiogenicandapoptoticeffectsofE7080.Conclusions:ResultsofthisstudyindicatethatE7080maybeagoodchoiceintreatmentofcolorectaltumors.FurthermoretheincreasedeffectsofE7080whencombinedwithL-NIOraisethepossibilitytousealowerdoseofE7080andthereforeavoid/minimizethesideeffectsobservedwithE7080.

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简介：Cancerevadeshostimmunesurveillancebyusingimmunecheckpoints,whichareinhibitorypathwayscrucialformaintainingself-tolerance1.Tumorcellsexpressmultipleinhibitoryligands,andtumor-infiltratinglymphocytes(TIL)expressavarietyofinhibitoryreceptors.InhibitoryreceptorscytotoxicT-lymphocyte-associatedprotein4(CTLA-4)andprogrammeddeath-1

简介：Objective:Tostudytheeffectofactivecompound6FandAfromPterissemipinnataL.(PsL)ontheactivitiesofDNAtopoisomerase(TOPO)IandII,activitiesofcytosolicandmembraneTPK,andexpressionofoncogenec-mycinlungadenocarcinomacells.Methods:Theeffectofcompound6FandAonactivitiesofcytosolicandmembraneTPKwasmeasuredbyscintillationcounting;theeffectofcompoundAonexpressionofoncogenec-mycwasdeterminedbyflowcytometryindirectfluorimetry.Results:compound6FandAcouldinhibittheactivitiesofTOPOI,andtheystronglyinhibitedtheTOPOIIin0.01mg/Land10.0mg/Lrespectively.CompoundAslightlyinhibitedtheactivitiesofmembraneTPK,butnotthecytosolicone.CompoundAcouldinhibittheexpressionofoncogenec-myc.Conclusion:Topoisomerasesaretargetofcompound6FandA.CompoundAcouldslightlyinhibittheactivitiesofTPK,andshowedaninhibitoryeffectontheexpressionofoncogenec-myc.

简介：Ameloblastomaisabenignbutlocallyaggressiveodontogenieneoplasmthataccountsfor10%ofalltumorsarisinginthemandibleandmaxilla(1).Eightypercentofameloblastomasariseinthemandible,andtheyareusuallyfoundinyoungadults.Itfrequentlyrecursifnotadequatelyresected.Therefore,thestandardtherapyforthistumoriscompleteboneresectionwithanadequatemarginofsafety:marginalorsegmentalosteotomy.However,aestheticdeformities,functionalimpairmentsandpsychologicalimpairmentsafterradicalsurgeryforlargeameloblastoma,havebeenseriousissues(1).

简介：Gastrointestinal(GI)cancerisoneofthemostcommoncausesofcancer-relateddeathsworldwide.Tumormarkersarevaluableindetectingpost-surgicalrecurrenceorinmonitoringresponsetochemotherapy.PyruvatekinaseisoformM2(PKM2),aglycolyticenzymecatalyzingconversionofphosphoenolpyruvate(PEP)topyruvate,confersagrowthadvantagetothetumorcellsandenablesthemtoadapttothetumormicroenvironment.Inthisreview,wehavesummarizedcurrentresearchontheexpressionandregulationofPKM2intumorcells,anditspotentialroleinGIcarcinogenesisandprogression.Furthermore,wehavealsodiscussedthepotentialofPKM2asadiagnosticandscreeningmarker,andatherapeutictargetinGIcancer.

简介：Objective:ToinvestigatetheeffectsofCAL-101,particularlywhencombinedwithbortezomib(BTZ)onmantlecelllymphoma(MCL)cells,andtoexploreitsrelativemechanisms.Methods:MTTassaywasappliedtodetecttheinhibitoryeffectsofdifferentconcentrationsofCAL-101.MCLcellsweredividedintofourgroups:controlgroup,CAL-101group,BTZgroup,andCAL-101/BTZgroup.TheexpressionofPI3K-p110σ,AKT,ERK,p-AKTandp-ERKweredetectedbyWesternblot.TheapoptosisratesofCAL-101group,BTZgroup,andcombinationgroupweredetectedbyflowcytometry.Thelocationchangesofnuclearfactorkappa-B(NF-κB)of4groupswasinvestigatedbyNF-κBKitexploring.Westernblotwasappliedtodetectthelevelsofcaspase-3andthephosphorylationofAKTindifferentgroups.Results:CAL-101dose-andtime-dependentlyinducedreductioninMCLcellviability.CAL-101combinedwithBTZenhancedthereductionincellviabilityandapoptosis.WesternblotanalysisshowedthatCAL-101significantlyblockedthePI3K/AKTandERKsignalingpathwayinMCLcells.ThecombinationtherapycontributedtotheinactivationofNF-κBandAKTinMCLcelllines.However,cleavedcaspase-3wasup-regulatedaftercombinedtreatment.Conclusion:OurstudyshowedthatPI3K/p110σisanoveltherapeutictargetinMCL,andtheunderlyingmechanismcouldbetheblockingofthePI3K/AKTandERKsignalingpathways.ThesefindingsprovidedabasisforclinicalevaluationofCAL-101andarationaleforitsapplicationincombinationtherapy,particularlywithBTZ.

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简介：Objective:Therecurrenceorprogressionunderendocrinetherapyinhormonereceptor-positive(HR+)advancedbreastcancer(ABC)remainedacriticalclinicalchallenge.Chidamideisanoralsubtype-selectivehistonedeacetylase(HDAC)inhibitorwithmultiplefunctionsintumorgrowthinhibitionandmicroenvironmentmodulationviaepigeneticreprogramming.Thepurposeofthisstudywastoevaluatethesafety,pharmacokinetics(PK),andpreliminaryefficacyofchidamideincombinationwithexemestaneinHR+ABCpatients.Methods:EligiblepatientswerepostmenopausalwomenwithHR+ABCrecurrentorprogressedtoatleastoneendocrinetherapy.Bloodsampleswereobtainedintherun-inperiodandthefirstdayofcombinationtreatmentforPKanalysis.Incombinationtreatment,patientsweregivenexemestane25mgdailyandchidamide30mgtwiceaweek(BIW)untilprogressionofdiseaseorintolerabletoxicities.Atreatmentcyclewasdefinedas4weeks.Safety,PKparameters,andpreliminaryefficacywereevaluated.Results:Atotalof20patientswereenrolledbetweenJulyandDecember,2015.Themediannumberoftreatmentscyclewas5.2(20.8weeks)with2patientsstillontreatmentatthedatacut-offdateofOctober,2017.Thetreatment-relatedadverseevents(AE)≥grade3inmorethan2patientswereneutropenia(35%),thrombocytopenia(30%),andleucopenia(20%).Theplasmaexposureofexemestanewasconsistentinthepresenceorabsenceofchidamide.Aslightincreaseinchidamideexposurewasnotedinthepresenceofexemestane,probablyduetotheinter-andintra-patientvariations.Thebestresponsein16evaluablepatientswasassessedbyResponseEvaluationCriteriainSolidTumors(RECIST),including4patientswithpartialresponse,10patientswithstabledisease.Themedianprogression-freesurvival(PFS)was7.6months.Conclusions:ThecombinationofchidamidewithexemestanewasgenerallywelltoleratedwithpromisingpreliminaryefficacyinHR+ABCpatients.Theoverallresultsfromthisstudyencouragefurtherpivotaltrialinthispatie