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Mechanical Studies on Treatment of Malignant Tumour by Ultralow Frequency Pulsed-Gradient Magnetic Fields

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Mechanical Studies on Treatment of Malignant Tumour by Ultralow Frequency Pulsed-Gradient Magnetic Fields

    Mechanical Studies on Treatment of

    Malignant Tumour by Ultralow Frequency

    Pulsed-Gradient Magnetic Fields

JOURNALOFNATURALSCIENCES

    ;ArticlelD:10071202(2003)02046304

    ;VoI.8No.2A2003,463.466

    ;MechanicalStudiesonTreatmentof

    ;MalignantTumourbyUltralowFreque.cy

    ;Pulsed?GradientMagneticFields

    ;DengRen-qing’,LiuQing-hua2

    ;ZhangHu-shengI

    ;1.CollegeofPhysicalScienceandTechnology,Wuhan ;University,Wuhan430072,Hubei,China;

    ;2.Departmentofelectricandcomputerengineering, ;NationalUniversityofSingapore,Singapore119260,Singa ;pore

    ;Abstract:Uhralowfrequency(UIF)pulsedgradient

    ;magneticfield(withthemaximumintensityof0.62.0T, ;gradientof10100T?m0.pulsewidthof20200msand

    ;frequencyof0.16-1.34Hz)treatmentofmicecaninhibit ;murinemalignanttumourgrowthandcaninduceapoptosisof ;cancercel1.Theapoptoticcancereellcontracted,became ;rounderanddivorcedfromadjacentcells;theheterochromatin ;condensedandcoagulatedtogetheralongtheinnersideofthe ;nuclearmembrane:theendoplasmicreticulumsexpandedand ;fusedwiththecellularmembrane;manyapoptoticbodies ;whichwerepackedbythecellularmembraneappearedand ;weredevouredbysomelymphocytesandplasma.ByIorentz ;forcethemagneticfieldkeepsthemovingionswithinbounds ;ofLarmorradius.Thus,penetratingcapabilityofthepositive ;andnegativeionsthroughthecellmembranewasaffected. ;eventheroleontheeel1membraneformed.

    ;Keywords:magneticfield;cancer;apoptosis;roleoncell ;membran

    ;CLCnumber:Q64

    ;Receiveddate:20020916

    ;Foundationitern:SupportedbytheNationalNaturalScienceFoun

    ;dationofChina(39870823)andtheMinistryofScienceandrlbchnolo ;gyofChina

    ;Biography:DengRenqing(1947),male,Associateprofessor.re ;searchdirection:electronicsandbiomagnetism.E-mail:rqdeng@whu. ;edu.cn

    ;0IntrOdUCtiOn

    ;Ieisiinipe.rdograe.s.sngonwtirehatgmeeantvmanaliegn.anttuiemnoeuranbdymeahg-

    ;nologyandthoroughstudiesofbiomagnetism.Forexample, ;Changetal.reportedthatpulsedmagneticfidd(0.8T,22 ;ms,1Hz)inhibitedthegrowthofS180sarccmainmice[,

    ;andusedthesamemagneticfieldstrengthtctreatpatients ;withmiddleandlatestagedisease.Nineof1}.casesshowed ;goodimprovement,and9werelesswellinhibited[. ;Since

    ;1987,GWo-llinhadtreatedeffectively50caEcereaseswith ;NdFe-Bpermanentmagnet(0.4T)[={].Magneticfieldtreat

    ;mentofmicecaninhibitmurinemalignanttumourgrowth,as ;seenfromanalysesatdifferenthierarchicallevels.fromorgan- ;ism,organ,totissue,anddowntocellandmacromolecules. ;However,becausethebiologicaleffectsofthemagneticfield ;andmechanismsareverycomplicated.furtherworksarestill ;needed.

    ;1Experimental

    ;1.1TreatmentofMiceinMagneticFields

    ;TwentyKunmingmiceofabout2monthsandweighing ;(3640g)werekeepedinsinglecageplacedaroom.thusliving ;conditions(food,water,temperature,light,air,etc)ofall ;themicehavethesame.Theywererandomlydividedinto2 ;groups.No.110weretreatedSamples,wkileNo.1120

    ;werecontrolsamples.Themicewereinoculate:lintheirright ;frontlegswith1×10S180sarcomaascitescells.Sarcomas

    ;463

    ;

    ;formed45daysafterinoculation.

    ;Thetreatedmicewereputinplexiglassboxeswithair ;holes.andlocatedonthemagneticcoilof10cmindim ;meterofacustomised(ELF)pulsedgradientmagnetic

    ;fieldgenerator.

    ;Whenpulsedelectriccurrentpassedthroughthe

    ;coil,themagneticfieldhadamaximumintensityof0.6

    ;2.0T,withagradientof10100Tpermetre,andthe

    ;pulsewidthwas2O200mswithafrequencyof0.16

    ;1.34Hzbeinggenerated.Thetreatedanimalswereex

    ;posedtothismagneticfieldfor15minperdayatroom

    ;temperature1826?,whilenotreatmentwasappliedto ;thecontrolsamples.Twentyeightdayslater,themice

    ;werekilledbycervicaldislocation,andthesarcomascut ;outandweighed.Sarcomaspecimenswerepreparedfor ;thefollowingexaminations.

    ;1.2OpticalSectionsandObservation

    ;Sarcomaswiththevolumeoflcm.werefixedin ;10%formalin,dehydratedthroughgradedalcohols, ;brightenedwithditolueneandsoakedinparaffinwaxin ;anincubatorat60.C.Theywerefinallyembeddedinpar

    ;affinwaxatroomtemperature.Sectionscutat3-4gm ;werestainedwithHE.Theywereexaminedmicro

    ;scopicallyat100and300magnifications.

    ;1.3TransmissionElectronMicroscope(TEM) ;Specimensofsarcomasofaboutlmm3werefixed. ;washed,postfixed,dehydrated,andembeddedconven

    ;tionallybeforebeingcutonanultramicrotomeatabout50 ;nm.Thesectionsweredouble-stainedwithleadcitrate ;anduranylacetonebeforebeingobservedinaHU-11A ;TEMat50kVacceleratingvoltage.

    ;1.4Detecting

    ;Labeling

    ;isThroughinsituNick-End-

    ;Terminaldeoxynucleotidyltransferase(TdT)medi

    ;atednickendlabeling(TUNEL)wasicerformedwiththe ;ApopAlertDNAFragmetationAssayKit,asinstructed ;byitsusermanual(CL()NTECH,USA).Briefly,for

    ;malin-fixed.paraffinembeddedcane(1rtissuesections ;weremountedonglassslidesE.Theparaffinwaxwas ;removedbyimmersingslidesinfreshxylenefollowedby ;100ethano1.Slidesweredehydratedthroughdescend

    ;ingconcentrationsofethanol(1o0%,5,85,70%, ;500A),fixedin4formaldehvde/PBS,washedwith ;PBS.andtreatedwithproteinaseK.Next,theslides ;wereincubatedwithbuffercontaining:!luorescenin-dUTP ;andTdTenzyme,andthecellsstainedwithpropidium ;iodide(PI),followedbyafinalwashi7iPBS.Theslides ;wereexaminedassoonaspossibleth(reafter.Apoptotic ;cellsexhibitedstronggreenunclearflJorescenceusinga ;standardfluoresceinfilterof(520?20)nm.Allcellsstai

    ;ningwithPIexhibitedstrongredc)toplasmicfluores

    ;cencewhenviewedatabout620nmL5j.

    ;2ResultsandDiscussion

    ;2.1MiceandSarcomas

    ;Thestatisticalresultsshowthatthemeanweightsof ;thetreatedmiceincreased1weekaft{?rtheexperiment. ;whilethemeanweightsofcontrolsdecreased,indicating ;thatthetreatedsamplesareinbette.rbodyconditions ;thanthecontrolones.Astatisticaldifferenceappeared ;within28days(Table1).

    ;Table1Comparisonofweightsofmiceandsarcomasoftreatedandcontrolgroup

    ;a)P%0.05.b)P%0.01.o’7.Meanvalue;SD.Standarddeviation

    ;2.2TEMObeservati0n

    ;Byusingtransmissionelectronmicroscopy,itwas ;foundthatthecancerceilsofthetreatedgroupshowed ;themorphologicalpropertiesofcellapoptosis:thecancer ;cellscontracted,becamerounderandweredivorcedfrom ;adjacentcells;theheterochromatincondensedandcoagu

    ;latedtogetheralongthenuclearmembrane;theendoplas

    ;micreticulumsexpandedandfusedwiththecellular ;membrane;manyapoptoticbodieswhichwerepackedby ;Colsarcomas

    ;?SD)/g

    ;6?0.43

    ;7?0.79

    ;thecellularmembraneappearedandweredevouredby ;somelymphocytesandplasma.

    ;Apoptosiscancerceilsoftreatedsamplebythemag

    ;neticfieldbecamerounderandwasdivorcedfromadjacent ;cells.Theendoplasmicreticulums(ER)inanapoptotic ;cancercellofthetreatedgrouphadmanyfoams.The ;heterochromatincoagulatedtogetheralongthenuclear ;membrane.Aholeofdimension0.4Lmappearedonthe ;cellularmembrane(1eft)(Fig.1).

    ;伸娜nen1

    ;

    ;

    ;

    ;planttothetwopolesandtwonewnueleiareformedE. ;Thetime-variedelectricfieldcanbeconsideredevenin ;thespaceofacell’srange.Theevenfieldgenerateda

    ;forcewithanequalquantityanddirectiontotheelectric ;particlesandblockedthesplitting.Becausethenucleusof ;thesarcomacellscarriedmorechargesandsplitmore ;quicklythanthenormalones,moreremarkableeffect ;wouldbecausedtoblocktheirmitoses.

    ;3Conclusions

    ;Inthispaper,wedeterminethemorphologyproper

;tiesofapoptosiscancercellsofthetreatedgroupbymag

    ;neticfield.andcoverforthefirsttimetheresultsthatthe ;holeofdimension0.4umappearedonthecellularmem

    ;braneofapoptosiscancercellsofthetreatedgroupby ;magneticfield.Furthermechanicalandclinicalresearchis ;muchneeded.Sinceuhraslowfrequencypulsed-gradient ;magneticfieldcaninduceapoptosisofcancercellandin

    ;hibitthegrowthanddivisionofmalignanttumour.itis ;feasibletouseitasanewmethodtotreatcancer. ;References

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    ;Acknowledgement:TheauthorsthankProf.LiTongping ;ofthePathologicalUnitofTongjiMelSchool,Hua[9]

    ;zhongUniversityofScienceTechnology.forhiskind ;instructionandhelp.

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