简介：Masterdevelopmentalpathways,suchasNotch,Wnt,andHedgehog,aresignalingsystemsthatcontrolproliferation,celldeath,motility,migration,andstemness.Thesesystemsarenotonlycommonlyactivatedinmanysolidtumors,wheretheydriveorcontributetocancerinitiation,butalsoinprimaryandmetastatictumordevelopment.Thereactivationofdevelopmentalpathwaysincancerstromafavorsthedevelopmentofcancerstemcellsandallowstheirmaintenance,indicatingthesesignalingpathwaysasparticularlyattractivetargetsforefficientanticancertherapies,especiallyinadvancedprimarytumorsandmetastaticcancers.Metastasisistheworstfeatureofcancerdevelopment.Thisfeatureresultsfromacascadeofeventsemergingfromthehijackingofepithelial-mesenchymaltransition,angiogenesis,migration,andinvasionbytransformingcellsandisassociatedwithpoorsurvival,drugresistance,andtumorrelapse.Inthepresentreview,wesummarizeanddiscussexperimentaldatasuggestingpivotalrolesfordevelopmentalpathwaysincancerdevelopmentandmetastasis,consideringthetherapeuticpotential.EmergingtargetedantimetastatictherapiesbasedonNotch,Wnt,andHedgehogpathwaysarealsodiscussed.

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简介：Consideringthegreatpotentialofnaturalproductsasanticanceragents,thepresentstudywasdesignedtoexplorethemolecularmechanismsresponsibleforanticanceractivitiesofMesuaferreastembarkextractagainsthumancolorectalcarcinoma.BasedonMTTassayresults,bioactivesub-fraction(SF-3)wasselectedforfurtherstudiesusingHCT116cells.Repeatedcolumnchromatographyresultedinisolationoflessactiveα-amyrinfromSF-3,whichwasidentifiedandcharacterizedbyGC-MSandHPLCmethods.α-amyrinandbetulinicacidcontentsofSF-3weremeasuredbyHPLCmethods.Fluorescentassaysrevealedcharacteristicapoptoticfeatures,includingcellshrinkage,nuclearcondensation,andmarkeddecreaseinmitochondrialmembranepotentialinSF-3treatedcells.Inaddition,increasedlevelsofcaspases-9and-3/7levelswerealsoobservedinSF-3treatedcells.SF-3showedpromisingantimetastaticpropertiesinmultipleinvitroassays.Multi-pathwayanalysisrevealedsignificantdown-regulationofWNT,HIF-1α,andEGFRwithsimultaneousup-regulationofp53,Myc/Max,andTGF-βsignallingpathwaysinSF-3treatedcells.Inaddition,promisinggrowthinhibitoryeffectswereobservedinSF-3treatedHCT116tumourspheroids,whichgiveahintaboutinvivoantitumorefficacyofSF-3phytoconstituents.Inconclusion,theseresultsdemonstratedthatanticancereffectsofSF-3towardscoloncancerarethroughmodulationofmultiplemolecularpathways.

简介：Non-smallcelllungcancer(NSCLC)ranksastheleadingcauseofcancer-relateddeathintheworld.Brainmetastasis(BM)isacommoncomplicationofNSCLC,with25%–40%ofpatientsdevelopingBMduringthecourseofthedisease.Asignificantstrategyoflocaldiseasecontrolinthecentralnervoussystemisradiationtherapy.Withthedevelopmentofprecisionmedicine,theconceptoftreatinglungcancerBMhasgraduallychanged.Inthiscase,weperformedasurgicalproceduretoobtainenoughtumortissueforthedetectionofthetargetgeneandotherrelatedexperimentsafterthepatientwasinformed.Finally,wefoundthatthepatienthadbothhepatocytegrowthfactorreceptor(MET)geneamplificationandkinesinlightchain1-anaplasticlymphomakinasefusion(KLC1-ALK)throughnext-generationsequencingandshowedsensitivitytothetargetedtherapyofcrizotinib.Thepatientexhibitedgoodresponse.Ourcasewassuccessfulandunderwenttargetedtherapywiththeguidanceofprecisediagnosis.