简介:AlkylatingagentsarechemicallyreactivedrugsthatreactwithDNAtoformcovalentbonds,causingsingle-strandordouble-strandDNAbreaksthatleadtointerstrandandintrastrandDNAcross-linking.Theseagentsareusedextensivelyincancerchemotherapy.Theyhaveasteepdose-responsecurveandarethereforeusefulindoseintensificationstrategies(e,g.inbonemarrowtransplantation).Thesubclassesofalkylatingagentsareasfollows.
简介:Mostcytotoxicchemotherapydrugsexerttheireffectbyinhibitingoneormoreoftheprocessesinvolvedincelldivision.Itappearsthatthefateofcellsdamagedbychemotherapyistodieprimarilybyinductionofapoptosis(prograrmnedcelldeath).Chemotherapyisgenerallyusedtotreatcanceratanadvancedorearlystage.
简介:现在的工作从marine-derivedstreptomyces学习化学成分3320~#并且他们的反肿瘤活动。酵素肉汤of3320~#的n-BuOH摘录在用antitoumor活动分开混合物的硅石胶化,SephadexLH-20,ODS列和HPLC上被用色层法分离。他们的结构用红外被识别,紫外,NMR,MSspectroscopic技术并且与出版数据相比。isolates的反肿瘤活动是用SRB方法和流动cytometry试金的assayed,对哺乳动物的tsFT210房间在轻显微镜下面与房间的词法观察伴随了。十混合物,出租机动三轮车--(翼列伊)1,出租机动三轮车--(Ala-Ile)2,出租机动三轮车--(Ala-Val)3,出租机动三轮车--(Phe-职业人员)4,出租机动三轮车--(Phe-Gly)5,出租机动三轮车--(列伊职业人员)6,1-methyl-1,2,3,4-tetrahydro-β-carboline-3-carboxylic酸7,N-(4-hydroxyphenethyl)乙酰胺8,4-methyoxy-1-(2-hydroxy)乙醇苯9并且uridine10,从streptomyces的酵素肉汤被孤立3320~#。在他们之中,加重6,7,8和10对有IC_(50)的tsFT210房间的显示出的有势力cytotoxicity3.6,7.2,5.2和1.6mmolL~珍视(-1),分别地。加重8,在2.0mmolL~下面的10也展出的apoptosis导致活动(-1)。混合物6,7,8和10是原则简历为海洋的streptomyces的theantitumor活动负责的活跃成分3320~#。化合物7第一次从这种被孤立。
简介:TagetonesA(1)andB(2),twonewmonocyclicditerpenoidswereisolatedfromthen-hexanefractionoffreshflowersofTagetesminutaL.(Asteraceae).Theirstructureswereestablishedbymultiplespectroscopicmethods(IR,HR-ESI-MS,and1D-,and2D-NMR),inadditiontocomparisonwithliteraturedata.Compound1showedcytotoxicactivitytowardsMCF7andA549cancercellswithIC_(50)valuesbeing4.68and4.24μmol·L~(-1),respectively,comparedtodoxorubicin(IC_(50)0.13and1.12μmol·L~(-1),respectively).Compound2alsoexhibitedsignificantactivityagainstHCT116cancercells(IC_(50),6.30μmol·L~(-1)).
简介:Marineorganismsaretheimportantsourceofthebioactivemetabolites.Anovelenolicsulfatedsterol,arenicolsterolA,hasbeenisolatedfromamarineannelidArenicolacristatacollectedinthecoastofMainlandofChina.ThestructurewaselucidatedusingallsortsofspectroscopicdataincludingESIMS,1Dand2DNMRetc.ThecytotoxicbioactivityofthissterolwasevaluatedbyMTTassay.Itcouldinhibitthegrowthofhumancervixcancercellline(Hela)andhumannon-smallcelllungcancercellline(NCI-h6)withIC50of(3.1+0.6)μg/mLand(7.6+0.8)μg/mL.
简介:benzothiazole衍生物的新系列被设计并且综合。最新综合的混合物对Escherichiacoli,葡萄球菌aureus和杆菌仙影拳为他们的抗菌剂活动被屏蔽。混合物6j和6o对E显示出最高的活动。coli和S。aureus。这些混合物的抗真菌的活动也对Candidaalbicans和曲霉属菌fumigatus被测试293。混合物4c,4g和6j对C展出了最高的活动。albicans。另外,混合物4a和6j对A显示了有希望的活动。fumigatus293。而混合物4a,6j和6p显示出中等活动,一样的混合物对ChromobacteriumviolaceumATCC12472为他们的察觉到antiquorum活动被检验。在里面综合混合物测试的vitrocytotoxicity对颈的癌症(Hela)和肾成纤维细胞癌症(COS-7)房间被执行线。结果显示所有测试混合物有IC50价值>50 ;对两根房间线的mol/L。分子的性质,毒性,药相似,和药获得混合物4a-c,5a,6g,h,6j,6l,6o和7c的侧面,d也被估计。
简介:ToinvestigatetheimbalancestateofhelperTlymphocytes(Th)andcytotoxicTlympho-cytes(Tc)andtherolesofTh1/Th2/Th3andTc1/Tc2cellsinrenaltransplantationrejection,theper-centagesofthesecellsinperipheralbloodof24casesofrenaltransplantationrecipientswithacutere-jectionandthedynamicchangesoftheCD4/CD8ratioweredeterminedbyflowcytometryanalysis,while30casesofhealthyindividualsweresetupascontrols.Inthesehealthycontrols,thepercentagesoftheTh1,Th2andTh3cellswere(10.45±8.15)%,(5.05±4.15)%and(3.90±3.21)%,andthoseofTc1andTc2cellswere(9.83±7.03)%and(4.51±2.17)%,respectively.However,thepercentagesofTh1andTclcellsinperipheralbloodofthestablerecipientsaftertransplantationwere(7.29±5.62)%and(7.04±5.15)%,showingdefinitereduction,whilethoseofTh2,Th3andTc2cellsshowedsignificantincrease,(6.34±5.67)%,(4.94±4.14)%and(6.86±4.42)%,respectively.Incaseofrecipientswithacuterejection,thepercentagesofTh1andTc1cellsappearedtobe(18.55±13.21)%and(15.84±11.72)%,alsoshowingsignificantincrease,butthoseofTh2,Th3andTc2cellsappearedtobereduced,(4.19±3.62)%,(3.02±2.83)%and(3.88±1.63)%,respectively.Significantdifferencescouldbedetectedamongthesethreegroups(P<0.05).TheCD4/CD8ratioincaseswithacuterejectionwashigherthanthoseofstablerecipients(2.24±0.59vs1.95±0.45),butthatofthestablerecipientsandhealthycontrols(1.98±0.31)showednoanysignificantdifference.Fromtheaboveobservation,itisevidentthatimbalancebetweenTh1,Th2andTh3withTc1andTc2cellsmayexistafterrenaltransplantationandprobably,theim-muneimbalancemaybeinducedthroughthesecretionofcytokinesINF-γbyTh1orTc1cells,Ⅱ-4byTh2andTc2cellsandTGF-βbyTh3.
简介:Anewcytotoxicpyrrolidinoindolinediketopiperazinedimer,cristatuminE(1),wasisolatedfromthefermentationbrothofthealgalfungusEurotiumherbariorumHT-2associatedwiththemarinealgae,Enteromorphaprolifera.ThestructurewasdeterminedbyspectroscopicanalysesandMarfey’saminoacidanalysis.CristatuminE(1)showedcytotoxicityagainstK562tumorcelllineandantibacterialactivityagainstEnterobacteraerogenesandEscherichiacoliwithIC50andMICvaluesof8.3,44.0and44.0mmol/L,respectively.
简介:TheaimofthepresentstudywastodeterminetheefficacyofimmunotherapywithdendriticcellstoelicitEBV-specificCTL-immunityinadvancedcasesofEBV-positivepatientswithnasopharyngealcarcinoma(NPC)andtodeterminethesafetyandtoxicityofthispreparation.NinecasesofhistologicallyconfirmedpatientswithNPCundergoingtreatmentwithradiologicaltherapywereenrolledinthisstudy.Dendriticcells,generatedinvitrofrombloodmonocytesofpatientswereculturedandmaturedwithcytokinesandtheninfectedwithrecombinantadenovirusvaccinecontainingEBV-latentmembraneprotein-2(Ad-LMP2).On9days'cultivationofcells,thematuredDCswereharvested,irradiatedwithCoandtheninjectedintradermallytopatientswithNPC.Theinjectionswereperformed3timestotally.Afterimmunization,theCTLresponseswereassayedbymeansofcytotoxicityandepitope-specificIFN-γproduction.Theresultsofthistrialshowedthatallpatientscouldtoleratethiskindoftreatmentwithoutanysideeffect,duringwhichmarkedincreaseofLMP2-specificCTL-responsescouldbedemonstratedin5patientsofthisgroup.AndthelevelofIgA/VCAantibodydecreasedin8of9patients,thusaccountingforabetterprognosisforthesepatients.Allpatientswillbefollowedupforanotheroneyear.Atleast,thepresentworkshowsthatintradermalvaccinationwithautologousDCsinfectedwithrecombinantAd-LMP2adenovirusisasafeprocedureinNPCpatients,inwhichthisprocedurecanenhancetheLMP2-specificCTLresponsesinpatients.Thesedataareencouragingtodevelopmoreeffectivevaccinestrategiesforthetreatmentofnasopharyngealcarcinoma.
简介:Interleukin-12(IL-12)isacriticalcytokinerepresentingthelinkbetweenthecellularandhumoralbranchesofhostimmunedefenseapparatus.IL-12-inducedcytotoxiclymphocyte(CTL)developmentisacentralmechanisminimmuneresponsesagainstintracellularinfectiousagentsaswellasmalignantgrowth.However,themolecularbasisoftumor-specificCTLresponsesmediatedbyIL-12remainspoorlydefined.Inthisstudy,weaddressedthisissueinacomprehensivemannertoprobeintoIL-12-inducedanti-tumorresponsesbyglobalgeneexpressionprofilingofmRNAexpressioninCD8+TcellsinatransplantablesyngeneicmousemammarycarcinomamodeltreatedornotwithrecombinantIL-12.AstrongtumorregressionwasinducedbytheIL-12treatment.AnintrospectionofdifferentialgeneexpressionatanearlystageoftheIL-12-initiatedCTLactivationrevealsinterestinggenesandmolecularpathwaysthatmayaccountforthemarkedtumorregression,andislikelytoprovidearichsourceofpotentialtargetsforfurtherresearchanddevelopmentofeffectivetherapeuticmodalities.Cellular&MolecularImmunology.2004;1(5):357-366.
简介:Inordertoelucidatethemolecularandimmunologicalmechanismsaswellasthepathogenesisofhemorrhagicfeverwithrenalsyndrome(HFRS),theCD8^+cytotoxicTlymphecytes(CTL)clonewasestablisheddirectlyfromperipheralbloodmononuclearcells(PBMC)ofpatientswithHFRS.TheactivitiesofCTLweredetectedasusualwithEBV-transformedlymphoblastoidcellline(BLCL)astargetcells.TheresultsshowedthattheCTLclonecouldrecognizedandkilledthetargetcellswithspecificityofnucleocapsidproteinofHantaanvirus(HTNVNP)withthecytotoxicitypercentagesof50.2%,25.4%and39.0%respectively.TheseresultsdemonstratedthattheantigenicepitopesofHTNVNPmainlylocatedontheC-temainaloftheviralnucleocapsidprotein.
简介:AbstractObjective:Pulmonary Mycobacterium tuberculosis infection can trigger cellular and humoral innate immune responses, which may cause death of the pathogen and or host cells/tissue. We aimed to determine the cytotoxic response of phagocytes in patients with pulmonary Mycobacterium tuberculosis infection based on plasma tumor necrosis factor-alpha (TNF-α), malondialdehyde (MDA), and superoxide dismutase (SOD) levels.Methods:In this observational study, patients newly infected with pulmonary Mycobacterium tuberculosis (n=31; age 37-62 years) and age-matched uninfected volunteers (n=50) were recruited as test and control volunteers, respectively in Owo, Nigeria. The study protocol was reviewed and approved by the Research and Ethics Committee of the Department of Medical Laboratory Science, Achievers University, Owo, Nigeria (AUO/MLS/VII/2009/212). Anti-hepatitis C virus, human immunodeficiency virus antigen/antibody, hepatitis B virus surface antigen, and plasma TNF-α were determined by enzyme-linked immunosorbent assay, SOD, and MDA were determined by colorimetry, Plasmodium by Giemsa thick blood film staining, and acid-fast bacilli in sputum were detected by Ziehl-Neelsen staining.Results:All participants had normal blood glucose levels and tested negative for human immunodeficiency virus antigen/antibody, anti-hepatitis C virus, hepatitis B virus surface antigen, and Plasmodium spp., and had no medical history of cancer. Infected patients had significantly higher plasma MDA and TNF-α levels and significantly lower SOD levels compared with control subjects (all P<0.05).Conclusion:Mycobacterium tuberculosis infection elicited a cytotoxic response by phagocytes, evidenced by significant increases in MDA and TNF-α and a significant decrease in SOD levels.