Specific Visualization of Glioma Cells in Living Low-Grade Tumor Tissue 英文参考文献.docVIP

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Specific Visualization of Glioma Cells in Living Low-Grade Tumor Tissue 英文参考文献.doc

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Specific Visualization of Glioma Cells in Living Low-Grade Tumor Tissue 英文参考文献

SpecificVisualizationofGliomaCellsinLivingLow-Grade TumorTissue SvenR.Kantelhardt1,WouterCaarls2,AnthonyH.B.deVries2,GuyM.Hagen2¤,ThomasM.Jovin2, WalterSchulz-Schaeffer3,VeitRohde1,AlfGiese1,DonnaJ.Arndt-Jovin2* 1Department of Neurosurgery, Georg-August-University of Go¨ttingen, Go¨ttingen, Germany, 2Laboratory of Cellular Dynamics, Max Planck Institute for Biophysical Chemistry,Go¨ttingen,Germany,3DepartmentofNeuropathology,Georg-August-UniversityofGo¨ttingen,Go¨ttingen,Germany Abstract Background: The current therapy of malignant gliomas is based on surgical resection, radio-chemotherapy and chemotherapy.Recentretrospectivecase-serieshavehighlightedthesignificanceoftheextentofresectionasaprognostic factorpredictingthecourseofthedisease.Completeresectioninlow-gradegliomasthatshownoMRI-enhancedimages areespeciallydifficult.Theaiminthisstudywastodeveloparobust,specific,newfluorescentprobeforgliomacellsthatis easytoapplytolivetumorbiopsiesandcouldidentifytumorcellsfromnormalbraincellsatalllevelsofmagnification. Methodology/PrincipalFindings:Inthisinvestigationweemployedbrightlyfluorescent,photostablequantumdots(QDs) to specifically target epidermal growth factor receptor (EGFR) that is upregulated in many gliomas. Living glioma and normalcellsortissuebiopsieswereincubatedwithQDscoupledtoEGFand/ormonoclonalantibodiesagainstEGFRfor30 minutes,washedandimaged.Thedataincluderesultsfromcell-culture,animalmodelandexvivohumantumorbiopsiesof both low-grade and high-grade gliomas and show high probe specificity. Tumor cells could be visualized from the macroscopictosinglecelllevelwithcontrastratiosashighas1000:1comparedtonormalbraintissue. Conclusions/Significance:Theabilityofthetargetedprobestoclearlydistinguishtumorcellsinlow-gradetumorbiopsies, where no enhanced MRI image was obtained, demonstrates the great potential of the method.We propose that future applicationofspecificallytargetedfluorescentparticlesduringsurgerycouldallowintraoperativeguidancefortheremoval ofresid