简介:AsanewmemberofIAP(inhibitorsofapoptosisprotein)family,survivinhaspotentanti-apoptoticactivities,andinvolvesinthemitosisandangiogenesis.Researcheshavedemonstratedthatsurvivingisatumor-specificanti-apoptoticfactor,expressedinfetaltissues,andcommonhumancancers,whilenotinnormal,terminallydifferentiatedadulttissues.Theoverexpressionofsurvivinintumortissuesiscorrelatedwithpoorprognosisofthepatients.Survivincanbeusedasaprognosticfactorandanewtargetintumortargetingtherapy.
简介:Thegeneralprinciplefortumorcellstoescapefromimmunesurveillanceistopreventtumorantigensfrombeingrecognizedbytheimmunesystem.Manymethodshavebeendevelopedtoincreasetheimmunogenecityofthetumorcells.Themostefficientmethodsareabletoforcetumorcellstopresenttheirowntumorantigenstotheimmunesystem.StimulatingThcellsbyconvertingtumorcellsintoMHCclassⅡ+/Ii-antigenpresentingcellsisoneofthemostefficienttechnologies.Usingantisensemethods,wesuppresstheexpressionoftheIiproteinthatnormallyco-expresseswithMHCclassⅡmoleculesandblockstheantigenicpeptidebindingsiteofMHCclassⅡmoleculesduringsynthesisintheendoplasmicreticulum.Insuchtumorcells,the'unprotected'MHCclassⅡmoleculespickupendogenoustumorantigenicpeptides,whichhavebeentransportedintotheERforbindingtoMHCclassⅠmolecules.SimultaneouspresentationoftumorantigensbybothMHCclassⅠandⅡmoleculesgeneratesarobustandlong-lastinganti-tumorimmuneresponse.MHCclassⅡ+/Ii-tumorcellsarepotenttumorcellvaccinesandalsocureasignificantnumberofanimalswithrenalandprostatetumors.Wehavedevelopedanalogoushumangenevectorsthataresuitableformostpatientsandcancers.
简介:Tumor-targetingantibodieswereinitiallydefinedasagroupoftherapeuticmonoclonalantibodies(mAb)thatrecognizetumor-specificmembraneproteins,blockcellsignaling,andinducetumor-killingthroughFc-driveninnateimmuneresponses.However,inthepastdecade,ampleevidencehasshownthattumor-targetingmAb(TTmAb)eradicatestumorcellsviaactivationofcytotoxicTcells(CTLs).Inthisreview,wespecificallyfocusonhowTTmAbsinduceadaptiveanti-tumorimmunityanditspotentialincombinationtherapywithimmunecytokines,checkpointblockade,radiation,andenzymetargetedsmallmoleculedrugs.ExploringthemechanismsofthesepreclinicalstudiesandretrospectiveclinicaldatawillsignificantlybenefitthedevelopmentofhighlyefficientandspecificTTmAb-orientedanti-tumorremedies.
简介:AbstractBackground:Previous evidence suggests inflammation may be a double-edged sword with cancer-promoting and cancer suppressing function. In this study, we explore the impact of local and systemic inflammation on cancer growth.Methods:Female BALB/C mice were subcutaneously implanted with foreign body (plastic plates) to build up a local inflammation and intraperitoneally injected with PolyIC or lipopolysaccharides (LPS) to build up a systemic inflammation, followed by subcutaneous injection of 5 × 105 colon cancer cells. Immunohistochemistry and enzyme linked immunosorbent assay were utilized to detect the Ki67 and interleukin (IL) 6, IL-1β, and monocyte chemoattractant protein-1 expression in thetumortissues and serum, respectively. The distributions of immune cells and expression of toll-like receptors (TLRs) were evaluated by flow cytometry (FCM) and quantitative real time-polymerase chain reaction.Results:The results showed that local inflammation induced by foreign body implantation suppressedtumorgrowth with decreasedtumorweight (P = 0.001), volume (P = 0.004) and Ki67 index (P < 0.001). Compared with the control group, myeloid-derived suppressive cells sharply decreased (P = 0.040), while CD4+ T cells slightly increased in thetumortissues of the group of foreign body-induced local inflammation (P = 0.035). Moreover, the number of M1 macrophages (P = 0.040) and expression of TLRs, especially TLR3 (P < 0.001) and TLR4 (P < 0.001), were significantly up-regulated in the foreign body group. Contrarily,tumorgrowth was significantly promoted in LPS or PolyIC-induced systemic inflammation (P = 0.009 and 0.006). FCM results showed M1 type macrophages (P = 0.017 and 0.006) and CD8+ T cells (P = 0.031 and 0.023) were decreased, while M2 type macrophages (P = 0.002 and 0.007) were significantly increased intumormicroenvironment of LPS or PolyIC-induced systemic inflammation group. In addition, the decreased expression of TLRs was detected in LPS or PolyIC group.Conclusions:The foreign body-induced local inflammation inhibitedtumorgrowth, while LPS or PolyIC-induced systemic inflammation promotedtumorgrowth. The results suggested that the different outcomes oftumorgrowth might be attributed to the infiltration of anti-tumoror pro-tumorimmune cells, especially M1 or M2 type macrophages intotumormicroenvironment.
简介:AbstractBackground:Hematopoietic stem cells (HSCs) have the ability to differentiate into all subsets of blood cells and self-renew. Largetumorsuppressor 1 (LATS1) and largetumorsuppressor 2 (LATS2) kinases are essential for cell cycle regulation, organism fitness, genome integrity, and cancer prevention. Here, we investigated whether Lats1 and Lats2 are critical for the maintenance of the self-renewal and quiescence capacities of HSCs in mice.Methods:Quantitative reverse transcription-polymerase chain reaction was used to determine the expression levels of Lats1 and Lats2 in subsets of progenitor cells and mature bone marrow cells. A clustered regularly interspaced short palindromic repeats system was used to generate Lats1 or Lats2 knockout mice. Complete blood cell counts were used to compare the absolute number of white blood cells, lymphocytes, monocytes, neutrophils, and platelets between Lats1 or Lats2 heterozygotes and littermates. Flow cytometry was used to assess the size of hematopoietic progenitor cells (HPCs) and HSC pools in Lats1 or Lats2 heterozygotes and littermates. The comparison between the two groups was analyzed using Student’s t test.Results:Lats1 and Lats2 were widely expressed in hematopoietic cells with higher expression levels in primitive hematopoietic cells than in mature cells. Lats1 or Lats2 knockout mice were generated, with the homozygotes showing embryonic lethality. The size of the HPC and HSC pools in Lats1 (HPC: wild-type [WT] vs. heterozygote, 220,426.77 ± 54,384.796 vs. 221,149.4 ± 42,688.29, P = 0.988; HSC: WT vs. heterozygote, 2498.932 ± 347.856 vs. 3249.763 ± 370.412, P = 0.105) or Lats2 (HPC: WT vs. heterozygote, 425,540.52 ± 99,721.86 vs. 467,127.8 ± 89,574.48, P = 0.527; HSC: WT vs. heterozygote, 4760.545 ± 1518.01 vs. 5327.437 ± 873.297, P = 0.502) heterozygotes were not impaired. Moreover, the depletion of Lats1 or Lats2 did not affect the overall survival of the heterozygotes (Lats1: P = 0.654; Lats2: P = 0.152).Conclusion:These results indicate that a single allele of Lats1 or Lats2 may be sufficient for normal hematopoiesis.
简介:Tumormetastasisisthedominantcauseofdeathincancerpatients.However,themolecularandcellularmechanismsunderlyingtumormetastasisarestillelusive.Theidentificationofproteinmoleculeswiththeirexpressionscorrelatedtothemetastaticprocesswouldhelptounderstandthemetastaticmechanismsandthusfacilitatethedevelopmentofstrategiesforthetherapeuticinterventionsandclinicalmanagementofcancer.Proteomicsisasystematicresearchapproachaimingtoprovidetheglobalcharacterizationofproteinexpressionandfunctionundergivenconditions.Proteomictechnologyhasbeenwidelyusedinbiomarkerdiscoveryandpathogeneticstudiesincludingtumormetastasis.Thisarticleprovidesabriefreviewoftheapplicationofproteomicsinidentifyingmolecularfactorsintumormetastasisprocess.Thecombinationofproteomicswithotherexperimentalapproachesinbiochemistry,cellbiology,moleculargeneticsandchemistry,togetherwiththedevelopmentofnewtechnologiesandimprovementsinexistingmethodologieswillcontinuetoextenditsapplicationinstudyingcancermetastasis.
简介:AbstractGlioblastoma (GBM) is the most common primary malignancy of the central nervous system in adults. The prognosis for late-stage glioblastoma (World Health Organization grade IV astrocytic glioma) is very poor. Novel treatment options are sought after and evaluated by clinicians and researchers, and remarkable advances have been made in surgical techniques, radiotherapy, and chemotherapy. However, the treatment of glioblastoma remains extremely difficult and it can extend the lives of patients by only a few months. There has been notable progress in the field of immunotherapy, particularly with the use oftumorvaccines, for treating glioblastoma; especially peptide vaccines and cell-based vaccines such as dendritic cell vaccines andtumorcell vaccines. However, the results of the current clinical trials for vaccination are not satisfactory. This article reviews the progress in the development of vaccines for glioblastoma.
简介:Someantitumoractivitiesofcomponent(E),extractedfromtherootofFagopynumCymosum(Trev)Meisn(FCTM),haverecentlybeendiscoveredinvivoandinvitro.ThecomponentE(CE)’spatternofactionwithtumorcellularDNAatthemolecularpharmacologicallevelwasinvestigatedbymacromolecularsynthesisexperiment(MSE)andhumanDNAinteractionsystemestablishedinourlaboratory.Theexperimentsdemonstratedthat,invitro,theagentcouldmarkedlyinhibittheincorporationof3H-TdRintothecellularDNA,andtheIC50inP388leukemiacellandinSGC-7901cellwas17.86μg/mland110.4μg/ml,respectively.Theagent,atmg/mllevel,couldproduceanintercalationreversionpatternwithDNAwithinashorttime(2hours).Butwhentheintervalwasprolongedforover4hours,theactionchangedtointercalationirreversiblepattern.Accordingtotheseobservations,theauthorsinferthatCEinteractswithDNAintwoways-directlyandindirectly.Theindirectaction,especiallyinlowconcentr
简介:Purposes:Wereportedtherolesandfunctionsofnursesinhomevisitsforbraintumorpatientsusingthefamilyhealthassessmentguideinthestudy.Methods:Onepatientofbraingliomawaschosenasthecaseillustration.Thenursesassessedthepatients’situation,theirfamiliesandlivingenvironmentindividually.Allthesefactorswereanalyzedtogether.Results:Thenursesthenimplementedtheirknowledgeandskillstoadoptdifferentmeasuresindifferentconditions,investigatedthepatients’healthproblemsandcarriedoutpersonalizedeffectiveactions.Conclusions:Nursesshouldputeffortintocommunitynursingtoallowpatientstoliveinasafeenvironment,tosatisfythehealthneedsofhumanbeingandtheirneedsforhealthknowledge,andenhancetheirself-careabilities.
简介:Interleukin-18(IL-18)wasdiscoveredasaninterferon-γ-inducingfactorandhadacriticalroleininflammatoryandimmuneresponse.Itstimulatesnaturalkiller(NK)andTcellsandenhancesTh1immuneresponse.Theseactivatedimmunecellseliminatecancercellsandvirus-infectedcellseffectively.However,IL-18hasalsobeenfoundtopromotetumorprogression.HigherexpressionorsecretionlevelofIL-18isdetectedinvariouscancercellsincomparisonwithnormalcontrol,andIL-18isabletoinduceangiogenesis,migration/metastasis,proliferationandimmuneescape.ThesedualeffectsandthemechanismofIL-18needtobeinvestigatedfurtherasitrelatestocancer.