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Feasibility and Limits of an Orthotopic Human Colon Cancer Model in Nude Mice

机译:裸鼠原位人类结肠癌模型的可行性和局限性

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Wesoughttodevelopanaccuratecolorectalcancermodelinnudemicewithstablelocalgrowth,tumorcelldissemination,andreproduciblemetastaticcapacity.Tothisend,weorthotopicallytransplantedhistologicallyintacthumancolorectalcancertissuefrom10humanpatientsintonudemice.Aftersuccessfullocaltumorgrowth,tumortissueswereretransplantedasmanyas9timesinserialpassage.Allspecimensweretransplantedusingmicrosurgicaltechniques.Histologic,immunohistochemical,andpolymerasechainreactiontechniqueswereusedtodeterminetumorgrowthratesandkinetics,developmentofregionallymphnodeanddistanthepaticmetastases,andtheinductionofminimalresidualdisease(MRD).Stablelocaltumorgrowthrateswithvariablegrowthkineticsweredetectedin73.4%ofallmice.Thelymphnodeandhepaticmetastasisrateswerelow,at18.4%and4.9%,respectively.MRD,asreflectedbyCK20positivityofthebonemarrowinanimalswithlymphnodeandhepaticmetastases,waspresentin22.2%.Theorthotopiccolorectalcancermodeldescribedhereisfeasiblefortheinductionofreproduciblelocaltumorgrowthbutislimitedbyvariablegrowthkineticsandthelowrateoflymphnodeandhepaticmetastases.Cytokeratin-positivecellsindicativeofMRDcouldbedetectedinthebonemarrowofapproximately25%ofthenudemicewithmetastases.TheobservedinductionofMRDafterorthotopicimplantationofintacthumancoloncancerinanimalswithlymphnodeandhepaticmetastasesmightbeimprovedifestablishedcoloncancercelllineswereused.
机译:Wesoughttodevelopanaccuratecolorectalcancermodelinnudemicewithstablelocalgrowth,tumorcelldissemination,andreproduciblemetastaticcapacity.Tothisend,weorthotopicallytransplantedhistologicallyintacthumancolorectalcancertissuefrom10humanpatientsintonudemice.Aftersuccessfullocaltumorgrowth,tumortissueswereretransplantedasmanyas9timesinserialpassage.Allspecimensweretransplantedusingmicrosurgicaltechniques.Histologic,免疫组织化学,andpolymerasechainreactiontechniqueswereusedtodeterminetumorgrowthratesandkinetics,developmentofregionallymphnodeanddistanthepaticmetastases,andtheinductionofminimalresidualdisease(MRD).Stablelocaltumorgrowthrateswithvariablegrowthkineticsweredetectedin73.4%ofallmice.Thelymphnodeandhepaticmetastasisrateswerelow,at18.4%and4.9%,respectively.MRD,由淋巴结和肝转移的骨髓动物的CK20阳性所反映的阳性率为22.2%。此处描述的原位结直肠癌模型可诱导可再生的局部肿瘤生长,但受血管的限制可能的生长动力学和较低的淋巴结转移率和肝转移率。可以在大约25%的转移率的骨髓中检测到指示MRD的细胞角蛋白阳性细胞。

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