High Interstitial Fluid Pressure Is Associated with Tumor-Line Specific Vascular Abnormalities in Human Melanoma Xenografts 英文参考文献.docVIP

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High Interstitial Fluid Pressure Is Associated with Tumor-Line Specific Vascular Abnormalities in Human Melanoma Xenografts 英文参考文献.doc

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High Interstitial Fluid Pressure Is Associated with Tumor-Line Specific Vascular Abnormalities in Human Melanoma Xenografts 英文参考文献

HighInterstitialFluidPressureIsAssociatedwithTumor- LineSpecificVascularAbnormalitiesinHuman MelanomaXenografts TrudeG.Simonsen*,Jon-VidarGaustad,MaritN.Leinaas,EinarK.Rofstad GroupofRadiationBiologyandTumorPhysiology,DepartmentofRadiationBiology,InstituteforCancerResearch,OsloUniversityHospital,Oslo,Norway Abstract Purpose: Interstitial fluid pressure (IFP) is highly elevated in many solid tumors. High IFP has been associated with low radiocurabilityandhighmetastaticfrequencyinhumanmelanomaxenograftsandwithpoorsurvivalafterradiationtherapy incervicalcancerpatients.Abnormalitiesintumorvascularnetworkshavebeenidentifiedasanimportantcauseofelevated tumor IFP. The aim of this study was to investigate the relationship between tumor IFP and the functional and morphologicalpropertiesoftumorvascularnetworks. MaterialsandMethods:A-07-GFPandR-18-GFPhumanmelanomasgrowingindorsalwindowchambersinBALB/cnu/nu mice were used as preclinical tumor models. Functional and morphological parameters of the vascular network were assessed from first-pass imaging movies and vascular maps recorded after intravenous bolus injection of 155-kDa tetramethylrhodamineisothiocyanate-labeleddextran.IFPwasmeasuredinthecenterofthetumorsusingaMillarcatheter. AngiogenicprofilesofA-07-GFPandR-18-GFPcellswereobtainedwithaquantitativePCRarray. Results:HighIFPwasassociatedwithlowgrowthrateandlowvasculardensityinA-07-GFPtumors,andwithhighgrowth rate and high vascular density in R-18-GFP tumors. A-07-GFP tumors showed chaotic and highly disorganized vascular networks,whileR-18-GFPtumorsshowedmoreorganizedvascularnetworkswithsupplyingarteriolesinthetumorcenter anddrainingvenulesinthetumorperiphery.Furthermore,A-07-GFPandR-18-GFPcellsdifferedsubstantiallyinangiogenic profiles.A-07-GFPtumorswithhighIFPshowedhighgeometricresistancetobloodflowduetohighvesseltortuosity.R-18- GFP tumors with high IFP showed high geometric resistance to blood flow due to a large number of narrow tumor capillaries. Conclusions:HighI