简介：Tumorgrowthandmetastasisareangiogenesis-dependent.Anti-angiogenictherapymaybeausefulapproachtocancertherapy.Thisreviewdiscussedtumorangiogenesisandimmunotherapyoftargetingtumorangiogenesisfromtwomainaspects:(1)activevaccinationtoinduceeffectiveanti-angiogenesisimmunity;(2)passiveimmunotherapywithanti-pro-angiogenicmoleculesrelevantantibody.Evidencefromtherecentyearssuggestedthatanti-angiogenictherapyshouldbeoneofthemostpromisingapproachestocancertherapy.

简介：Matrixmetalloproteinases(MMPs)andtissueinhibitorsofmetalloproteinases(TIMPs)playasignificantroleinregulatingangiogenesis,theprocessofnewbloodvesselformation.Interstitialcollagenase(MMP-1),72kDagelatinaseA/typeIVcollagenase(MMP-2),and92kDAgelatinaseB/typeIVcollagenase(MMP-9)dissolveextracellularmatrix(ECM)andmayinitiateandpromoteangiogenesis.TIMP-1,TIMP-2,TIMP-3,andpossibly,TIMP-4inhibitneovascularization.Anewparadignisemergingthatmatrilysin(MMP-7),MMP-9,andmetalloelastase(MMP-12)mayblockangiogenesisbyconvertingplasminogentoangiostatin,whichisoneofthemostpotentangiogenesisantagonists.MMPsandTIMPsplayacomplexroleinregulatingangiogenesis.Anunderstandingofthebiochemicalandcellularpathwaysandmechanismsofangiogenesiswillprovideimportantinformationtoallowthecontrolofangiogenesis,e.g.thestimulationofangiogenesisforcoronarycollateralcirculationformation;whiletheinhibitionfortreatingarthritisandcancer.

简介：Angiogenesis是一个很复杂的生理的过程，它包含依赖于在生长因素(激发器和禁止者)之间的homeostatic平衡的多重小径。这个紧控制的过程被angiogenic因素刺激，它在肿瘤以内是在场的并且包围联系肿瘤的stromal房间。angiogenesis上的肿瘤繁殖，侵略和转移的依赖为对待恶意使新血容器形成的禁止者成为吸引人的药。Angiogenesis能被几不同机制破坏：由禁止endothelial房间，由打断发信号的小径或由禁止angiogenesis的另外的使活跃之物。这策略在稳固的肿瘤的几种类型显示出治疗学的利益，导致食物药品管理局(食物及药品管理局)在肾，非小的房间肺，结肠和大脑的治疗的anti-angiogenic代理人的赞同癌症。尽管没有angiogenesis禁止者与变形前列腺癌症为病人被同意了，指向新血容器形成的治疗仍然是前列腺癌症研究的一个新兴、有希望的区域。

简介：Thispaperproposesamorerealisticmathematicalsimulationmethodtoinvestigatethedynamicprocessoftumourangio-genesisbyfullycouplingthevesselgrowth,tumourgrowthandassociatedbloodperfusion.Thetumourgrowthandangiogenesisarecoupledbythechemicalmicroenvironmentandthecell-matrixinteraction.Thehaemodynamiccalculationiscarriedoutonthenewvasculature,andanestimationofvesselcollapseismadeaccordingtothewallshearstresscriterion.Theresultsareconsistentwithphy...

简介：AbstractEndometriosis (EM) is a benign gynecological disease that affects the fertility and health of women of reproductive age; it is characterized by the presence of endometrial glands and stroma outside the uterine cavity. Although several hypotheses have been proposed to explain the underlying cause of EM, its pathogenesis remains obscure. Recently, non-coding RNAs were reported to be involved in the occurrence and development of EM. MicroRNAs and long non-coding RNAs are the main members of the non-coding RNA family that contribute to EM progression in various aspects, such as cell proliferation, apoptosis, invasion, and angiogenesis. Angiogenesis plays a pivotal role in the initiation and development of EM and provides a substantial background for the invasion, proliferation, and long-term growth of endometriotic implants. This review aimed to investigate the role of microRNAs and long non-coding RNAs in regulating angiogenesis in EM and discuss how this mechanism can be used for diagnostic and therapeutic purposes in EM.

简介：Erythroprotein-producinghumanhepatocellularcarcinomareceptors(Ephreceptors)composeasubfamilyoftransmembraneprotein-tyrosinekinasesreceptorsthattakespartinnumerousphysiologicalandpathologicalprocesses.Ephfamilyreceptor-interactingproteins(Ephrins)areligandsforthosereceptors.Eph/ephrinsystemisresponsibleforthecytoskeletonactivity,celladhesion,intercellularconnection,cellularshapeaswellascellmotility.Itaffectsneurondevelopmentandfunctioning,boneandglucosehomeostasis,immunesystemandcorrectfunctionofenterocytes.MoreoverEph/ephrinsystemisoneofthecrucialonesinangiogenesisandlymphangiogenesis.Withsuchawiderangeofimpactitisclearthatdisturbedfunctionofthissystemleadstopathology.Eph/ephrinsystemisinvolvedincarcinogenesisandcancerprogression.Althoughtheideaofparticipationofephrinincarcinogenesisisobvious,theexactwayremainsunclearbecauseofcomplexbi-directionalsignalingandcross-talkswithotherpathways.Furtherstudiesarenecessarytofindanewtargetfortreatment.

简介：Angiogenesis在出生后的生命期间在胚胎的脉管的树的发展以及处于几个正常、病理学的条件起一个基本作用。Bloodsupply，由neovascularization建立了，在愈合弯屈期间为histogenesis是必要的以及变长的手足在骨胳的损伤sequalae的治疗广泛地适用。Butlittle注意对这个区域被给予了。这评论试图在机械应力下面总结angiogenesis规定，在愈合的创伤中的angiogenesis的过程和angiogenesis，特别地与紧张压力原则联合。

简介：ShouwuisatraditionalChinesemedicine(TCM)withneuroprotectiveeffect.ShouwuYizhidecoction(SYD)wasdesignedbasedonTCMtheory.However,littleisknownabouttherolesofSYDinVasculardementia(VaD).ThepresentstudyaimedtoevaluatethepotentialeffectsofSYDonthevascularcognitiveimpairmentandexploretheunderlyingmechanismbyestablishingfocalcerebralischemia/reperfusion(I/R)ratmodeltoinduceVaD.SYDadministration(54mg·kg~(-1))for40daysobviouslyimprovedthevascularcognitiveimpairmentinthemiddlecerebralarteryocclusion(MCAO)ratsasevidencedbythedeclinedneurologicaldeficitscoreandshortenedescapelatencyvianeurologicaldeficitassessmentandMorriswatermazetest.Moreover,SYDdecreasedneurondamage-inducedcelldeathandamelioratedtheultrastructureofendothelialcellsintheMCAOrats,therebyalleviatingVaD.Mechanistically,SYDcausedincreasesintheexpressionofvascularendothelialgrowthfactor(VEGF),CD34andCD31,comparedwiththeMCAOratsincoronalhippocampus.Simultaneously,theexpressionlevelofmiR-210waselevatedsignificantlyafterSYDadministration,comparedwiththevehiclerats(P<0.01).TheexpressionofNotch4atbothmRNAandproteinlevelswasupregulatedremarkablyalongwiththenotablydownregulatedDLL4expressionunderSYDadministrationcomparedwiththevehiclerats(P<0.05).Overall,theaboveresultsindicatedthatSYDpromotedangiogenesisbyupregulatingVEGF-inducedmiR210expressiontoactivateNotchpathway,andfurtheralleviatedneurondamageandamelioratedtheultrastructureofendothelialcellsintheMCAOrats,ultimatelyenhancingthecognitionandmemoryofMCAOrats.Therefore,ourfindingspreliminarilyidentifiedtheeffectandthemechanismofactionforSYDonVaDinrats.SYDcouldbeapotentialcandidateintreatmentofVaD.

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简介：AbstractBackground:Angiogenesis and hypoxia-inducible factor 1α (HIF-1α) play major roles in solid tumors. This study aimed to establish a longitudinal and multimodal imaging model for in vivo evaluation of HIF1α and angiogenesis in breast cancer.Methods:By transfection of a 5 hypoxia-responsive element (HRE)/green fluorescent protein (GFP) plasmid, the cell line Ca761-hregfp was established, which emitted green fluorescence triggered by HIF-1α under hypoxia. The cells were subjected to CoCl2-simulated hypoxia to confirm the imaging strategy. We grew Ca761-hre-gfp cells in the left rear flanks of twelve 615 mice. Experiments were conducted on days 4, 9, 15, and 19. For in vivo analysis, Ca761-hre-gfp subcutaneous allografted tumors were imaged in vivo using contrast-enhanced ultrasound (CEUS) and fluorescence imaging (FLI) during tumor development. The tumor size, CEUS peak intensity, and FLI photons were measured to evaluate tumor growth, angiogenesis, and HIF-1α activity, respectively. After each experiment, three mice were randomly sacrificed and tumor specimens were collected to examine HIF-1α activity and the microvessel density (MVD).Results:In vitro, both green fluorescence and HIF-1α expression were detected in Ca761-hre-gfp cells treated with CoCl2, indicating the suitability of the cells to detect HIF-1α activity. In vivo, HIF-1α activity first increased and then decreased, which was significantly correlated with angiogenic changes (r = 0.803, P = 0.005). These changes were confirmed by immunohistochemical staining of HIF-1α and MVD.Conclusions:The findings validated the Ca761-hre-gfp murine allograft model for reliable evaluation of HIF-1α activity and angiogenesis longitudinally using both molecular and pre-clinical non-invasive imaging modalities. The cell line may be useful for studies of anti-HIF pathway therapies.

简介：Objective:Toanalyzetheexpressionofinduciblenitricoxidesynthase(iNOS),endothelialnitricoxidesynthase(eNOS)andvascularendothelialgrowthfactor(VEGF)inhepatocellularcarcinoma(HCC)anditsrelationtoangiogenesis.Methods:Tissuesectionsfrom71HCCpatientswereexaminedimmunohistochemicallyforproteinexpressionofiNOS,eNOS,andVEGF.Microvessaldensity(MVD)wascountedbyendothelialcellsimmunostainedbyanti-CD34antibody.Results:PositiveimmunostainingforiNOS,eNOSwasdetectedin83.1%and85.9%ofHCCrespectively.INOSandeNOSwerenotdetectedinnormalhepatictissue.MVDwas34.3±1.5/HPand38.6±1.6/HPinHCCwithpositivestainingforiNOSandVEGFwhileitwas31.2±2.8/HP,and22.4±2.0/HPinHCCwithnegativestainingforiNOSandVEGF(P<0.01).AcorrelationbetweenNOSexpressionandVEGFinHCCwasnotobserved.Conclusion:iNOSandeNOSmayplayaroleinmalignanttransformationfpost-hepaticcirrhosis.TheexpressionofiNOSandVEGFfavorsangiogenesisofHCC.

简介：AIM:Tostudythepossibleactionsandmechanismsofperoxisomeproliferator-activatedreceptorγ(PPARγ),aligand-activatedtranscriptionfactor,inpancreaticcarcinogenesis,especiallyinangiogenesis.METHODS:ExpressionsofPPARγandretinoidacidreceptor(RXRα)wereexaminedbyreverse-transcriptionpolymerasechainreaction(RT-PCR)withimmunocytochemicalstaining.Pancreaticcarcinomacells,PANC-1,weretreatedeitherwith9-cis-RA,aligandofRXRα,orwith15-deoxy-Δ12,14prostaglandinJ2(15d-PGJ2),aligandofPPARγ,orboth.Antiproliferativeeffectwasevaluatedbycellviabilityusingmethyltetrazolium(MTT)assay.ApancreaticcarcinomaxenografttumormodelofnudemicewasestablishedbyinoculatingPANC-1cellssubcutaneously.Rosiglitazone,aspecificligandofPPARγ,wasadministeredviawaterdrinkinginexperimentalgroupofnudemice.After75d,allmiceweresacrificed.Expressionofproliferatingcellnuclearantigen(PCNA)intumortissuewasexaminedwithimmunohistochemicalstaining.Expressionofvascularendothelialgrowthfactor(VEGF)mRNAinPANC-1cells,whichweretreatedwith15d-PGJ2or9-cis-RAatvariousconcentrationsordifferentduration,wasdetectedbysemi-quantitativeRT-PCR.EffectsofRosiglitazoneonchangesofmicrovasculardensity(MVD)andVEGFexpressionwereinvestigatedinxenografttumortissue.Neovasculaturewasdetectedwithimmunohistochemistrystaininglabeledwithanti-Ⅳcollagenantibody,andindicatedbyMVD.RESULTS:RT-PCRandimmunocytochemicalstainingshowedthatPPARγandRXRαwereexpressedinPANC-1cellsatbothtranscriptionlevelandtranslationlevel.MTTassaydemonstratedthat15d-PGJ2,9-cis-RAandtheircombinationinhibitedthegrowthofPANC-1cellsinadose-dependentmanner.9-cis-RAhadacombinedinhibitingactionwith15d-PGJ2onthegrowthofpancreaticcarcinoma.InvivostudiesrevealedthatRosiglitazonesignificantlysuppressedthegrowthofpancreaticcarcinomaascomparedtocontrolgroup(0.48±0.23cm3vs2.488±0.59cm3,P<0.05),andthegro

简介：Objective:Tostudytherelationshipbetweencyclooxygenase-2(COX-2)expressionandtumorangiogenesisinhumanbreastcancer.Methods:Archivalprimarybreastcarcinomas(n=62),adjacentductalcarcinomainsitu(DCIS,n=13)andDCISalone(n=5)wereanalyzedforCOX-2andVEGFexpressionbyimmunohistochemistryusingspecificmonoclonalantibodies.Microvesseldensity(MVD)wasalsoexaminedtheusingCD34staining.Results:AsignificantcorrelationwasfoundbetweenCOX-2andVEGFexpression(P<0.01).BothCOX-2andVEGFweresignificantlycorrelatedwithMVD(P<0.05)andP<0.01,respectively).COX-2andVEGFgeneswereoverexpressedintumorspecimensascomparedwithnormalepithelia.Conclusion:COX-2isrelatedtotumorangiogenesisinbreastcancer.ItislikelythatVEGFisoneofthemostimportantmediatorsoftheCOX-2angiogenicpathway.

简介：AIM:Todeterminetheexpressionsofinduciblenitricoxidesynthase(iNOS)andmatrixmetalloproteinase-9(MMP-9)inhepatocellularcarcinoma(HCC)andtoinvestigatetherelationshipbetweeniNOSandMMP-9expressionandtheireffectsonangiogenesisandprogressionofHCC.METHODS:Tnthisstudy,weexaminediNOS,MMP-9,andCD34expressioninspecimenssurgicallyremovedfrom32HCCpatientsand7normallivertissuesbyimmunohistochemicalstaining.Meanwhile,microvesseldensity(MVD)wasdeterminedasamarkerofangiogenesisbycountingCD34-positivecells.RESULTS:ThepositiveratesofiNOSandMMP-9expressionwere71.88%(23/32)and78.13%(25/32)inHCC.MMP-gexpressionwassignificantlycorrelatedwithtumorsize,capsulestatus,TNMstage,andriskofHCCrecurrence(P=0.032,P=0.033,P=0.007,andP=0.001,respectively).TherewasalsoasignificantrelationshipbetweeniNOSexpressionandcapsulestatusandriskofHCCrecurrence(P=0.04gandP=0.004,respectively),butnocorrelationbetweeniNOSexpressionandtumorsizeandTNMstage.TherewasapositiveassociationbetweenMVDandTNMstageandriskofHCCrecurrence(P=0.037andP=0.000,respectively).ThecountofMVDwassignificantlydifferentindifferentiNOSandMMP-9immunoreactivitygroups(F=17.713and17.097,P=0.000andP=0.000,respectively).TheexaminationofSpearman'srankcorrelationcoefficientshowedthattherewasasignificantpositivecorrelationbetweenMVDandiNOS,MMP-9immunoreactivity(r=0.754and0.751,P=0.000andP=0.000,respectively).TherewasalsoasignificantassociationbetweenMMP-9andiNOSexpressioninHCC(P=0.010).CONCLUSION:Nitricoxide(NO)producedbyiNOScouldmodulateMMP-9productionandthereforecontributetotumorcellangiogenesisandinvasionandmetastasisinHCC.ThestrongexpressionofiNOSandMMP-9inHCCmaybehelpfulinevaluatingtherecurrenceofHCC,predictingpoorprognosis.ForpatientswithstrongexpressionofMMP-9andiNOS,theoptimaltreatmentschemen

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简介：Angiogenesisintheinfarctperipherycanimprovebloodflow.Vascularendothelialgrowthfactor(VEGF)hasbeenconsideredapotentialtherapeutictargetforstroke.BuyangHuanwudecoction(BYHWD)isaclassictraditionalformulaintraditionalChinesemedicineandisusedtotreatstroke;inaddition,thepromotioneffectsonVEGFproteinexpressionhavebeenconfirmed.However,littleisknownabouthowBYHWDregulatesangiogenesis,orabouttheeffectsofBYHWDonVEGFmRNAexpression.Forthisreason,thepresentstudymeasuredmicrovesseldensityinratswithcerebralischemiausingimmunohistochemistry.Inaddition,VEGFexpressionwasmeasuredbyreverse-transcriptionpolymerasechainreactionandenzyme-linkedimmunosorbentassaytode-terminetheeffectsofBYHWDonangiogenesisandVEGFexpressioninratswithcerebralischemia.Resultsdemonstratedthatmicrovesseldensity,aswellasVEGFmRNAandproteinexpression,increasedafter7and14daysofBYHWDtreatment,whichsuggeststhatBYHWDpromotedan-giogenesisfollowingcerebralischemiaandupregulatedVEGFmRNAandproteinexpressioninischemiccerebralregions.

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简介：Toinvestigatetheinhibitingeffectsoftheanti-angiogenicfactorandostatinandtheanti-angiogenicdrugendostatinontumourangiogenesisandtumourcells,acoupledmathematicalmodeloftumorangiogenesiswithtumourgrowthandbloodperfusionisdeveloped.Simulationresultsshowthatangiostatinandendostatincanimprovetheabnormalmicroenvironmentinsidethetumourtissuebyeffectivelyinhibitingtheprocessoftumorangiogenesisanddecreasingtumourcells.Thepresentmodelcanbeusedasavalidtheoreticalmethodintheinvestigationofthetumouranti-angiogenictherapy.

简介：AbstractBackground:Uveal melanoma (UM) is the most common primary intraocular malignancy in adults. It has been demonstrated that microRNA-145 (miR-145) is correlated with the progression of various cancers by regulating the expression of multiple target genes, especially a number of genes that regulate angiogenesis and proliferation. However, the underlying mechanisms of miR-145 in tumor angiogenesis of UM are still not well illustrated. Thus, we aimed to explore the potential target genes or pathways regulated by miR-145 in UM and the effect of miR-145 on invasion and angiogenesis.Methods:Totally, 24 choroid samples were collected in our study, including 12 UM samples and 12 normal uveal tissues. The expression of neuroblastoma RAS viral oncogene homolog (N-RAS), phosphorylated protein kinase B (p-AKT), and vascular endothelial growth factor (VEGF) in UM tissues and normal uveal tissues was analyzed using Western blotting analysis. Lentivirus expression system was used to construct MUM-2B and OCM-1 cell lines with stable overexpression of miR-145. Transwell and endothelial cell tube formation assay were used to measure the effects of miR-145 on the invasion and angiogenesis of UM in vitro. The downstream target genes of miR-145 were predicted by bioinformatics and confirmed using a luciferase assay. BALB/c nude mice models were established to investigate the mechanisms of miR-145 on tumor growth and angiogenesis in vivo. Group data comparisons were performed using analysis of Student’s t test. A two-tailed P < 0.05 was considered as statistically significant.Results:The results of Western blotting analysis indicated that the expressions of N-RAS (1.10 ± 0.35 vs. 0.41 ± 0.36, t = 3.997, P = 0.012), p-AKT (1.16 ± 0.22 vs. 0.57 ± 0.03, t = 7.05, P = 0.001), and VEGF (0.97 ± 0.32 vs. 0.45 ± 0.21, t = 3.314, P = 0.008) in UM tumor tissues were significantly higher than those in normal uveal tissue. Luciferase assay demonstrated N-RAS and VEGF as downstream targets of miR-145. Moreover, tube formation assay revealed that miR-145-transfected human microvascular endothelial cell line formed shorter tube length (36.10 ± 1.51 mm vs. 42.91 ± 0.94 mm, t = 6.603, P = 0.003) and less branch points (350.00 ± 19.97 vs. 406.67 ± 17.62, t = 3.685, P = 0.021) as compared with controls. In addition, the numbers of invaded MUM-2B and OCM-1 cells with miR-145 overexpression were significantly lower than the controls (35.7 ± 3.3 vs. 279.1 ± 4.9, t = 273.75, P < 0.001 and 69.5 ± 4.4 vs. 95.6 ± 4.7, t = 21.27, P < 0.001, respectively). In vivo, xenografts expressing miR-145 had smaller sizes (miR-145 vs. miR-scr, 717.41 ± 502.62 mm3vs. 1694.80 ± 904.33 mm3, t = 2.314, P = 0.045) and lower weights (miR-145 vs. miR-scr, 0.74 ± 0.46 g vs. 1.65 ± 0.85 g, t = 2.295, P = 0.045).Conclusion:Our results indicated that miR-145 is an important tumor suppressor and the inhibitory strategies against N-RAS/VEGF signaling pathway might be potential therapeutic applications for UM in the future.

简介：AIM:Toinvestigatetheassociationofcyclooxygenase-2(COX-2)expressionwithangiogenesisandthenumberandtypeofinflammatorycells(macrophages/Kupffercells;mastcells)withinprimaryhepatocellularcarcinoma(HCC)tissuesandadjacentnon-tumorous(MT)tissues.METHODS:ImmunohistochemistryforCOX-2,CD34,CD68andmastcelltryptase(MCT)wasperformedon14well-characterizedseriesofliver-cirrhosis-associatedHCCpatients.COX-2expressionandthenumberofinflammatorycellsintumorlesionsandsurroundinglivertissuesofeachspecimenwerecompared.Moreover,COX-2,CD34stainingandthenumberofinflammatorycellsinareaswithdifferenthistologicaldegreeswithineachtumorsamplewerecomparativelyanalyzed.RESULTS:ThepercentageofCOX-2positivecellswassignificantlyhigherinNTtissuesthanintumors.COX-2expressionwashigherinwell-differentiatedHCCthaninpoorly-differentiatedtissues.Fewmastcellswereobservedwithinthetumormass,whereasahighernumberwasobservedinthesurroundingtissue,especiallyinperi-portalspacesofNTtissues.Abundantmacrophages/KupffercellswereobservedinNTtissues,whereasthenumberofcellswassignificantlylowerinthetumormass.However,ahighercellnumberwasobservedinthewell-differentiatedtumorandprogressivelydecreasedinrelationtothedifferentiationgrade.Withinthetumor,apositivecorrelationwasfoundbetweenCOX-2expressionandthenumberofmacrophages/Kupffercellsandmastcells.Moreover,therewasapositivecorrelationbetweenCD34andCOX-2expressionintumortissues.Comparisonbetweenwell-andpoorly-differentiatedHCCshowedthatthenumberofCD34-positivecellsdecreasedwithdedifferentiation.However,COX-2wastheonlyindependentvariableshowingapositivecorrelationwithCD34inamultivariateanalysis.CONCLUSION:ThepresenceofinflammatorycellsandCOX-2expressioninlivertumorsuggestsapossiblerelationshipwithtumorangiogenesis.COX-2expressingcellsandthenumberofmacro