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利用磁共振成像(MRI)在鸡胚尿囊膜上原位生长的不同肿瘤移植物中探究血管反应性和缺氧表型。

Probing Vasoreactivity and Hypoxic Phenotype in Different Tumor Grafts Grown on the Chorioallantoic Membrane of the Chicken Embryo In Ovo Using MRI.

作者信息

Buschmann Johanna, Heuberger Dorothea M, Kivrak Pfiffner Fatma, Wolint Petra, Jang Jae-Hwi, Jungraithmayr Wolfgang, Giovanoli Pietro, Calcagni Maurizio, Waschkies Conny F

机构信息

Center for Surgical Research, University Hospital Zurich, 8091 Zurich, Switzerland.

Plastic Surgery and Hand Surgery, University Hospital Zurich, 8091 Zurich, Switzerland.

出版信息

Cancers (Basel). 2022 Jun 25;14(13):3114. doi: 10.3390/cancers14133114.

Abstract

Tumor grafts grown on the chorioallantoic membrane (CAM) of chicken embryos represent a transition between cell culture and mammalian in vivo models. Magnetic resonance imaging (MRI) started to harness this potential. Functional gas challenge is feasible on the CAM. Using quantitative T1 and T2* mapping, we characterized the response of MC-38 colon, A549, and H460 adeno-carcinoma cell grafts to hypercapnic (HC) and hypercapnic-hyperoxic (HCHO) gas challenges, pertaining to the grafts' vascular and oxygenation phenotypes. MR imaging revealed that larger T1 and T2* were located in the center of H460 and MC-38 tumors. Quantitative analysis showed a significant reduction in T1 and a significant increase in T2* in response to HCHO for A549 grafts, while H460 and MC-38 tumors did not respond to either gas challenge. Different tumor grafts respond differentially to HC and HCHO conditions. A549 tumor grafts, with higher vessel density and smaller tumor diameter compared with H460 and MC-38 grafts, had a significant response in T1 for HCHO and T2* increased slightly during HC and significantly under HCHO, consistent with a normoxic phenotype and functional vasoreactivity. Therefore, gas challenges enable differential characterization of tumor grafts with respect to their vascular and oxygenation status.

摘要

在鸡胚绒毛尿囊膜(CAM)上生长的肿瘤移植物代表了细胞培养和哺乳动物体内模型之间的一种过渡。磁共振成像(MRI)开始利用这一潜力。在CAM上进行功能性气体激发是可行的。利用定量T1和T2映射,我们表征了MC-38结肠癌、A549和H460腺癌细胞移植物对高碳酸血症(HC)和高碳酸血症-高氧血症(HCHO)气体激发的反应,这与移植物的血管和氧合表型有关。磁共振成像显示,较大的T1和T2位于H460和MC-38肿瘤的中心。定量分析表明,A549移植物对HCHO反应时T1显著降低,T2显著增加,而H460和MC-38肿瘤对两种气体激发均无反应。不同的肿瘤移植物对HC和HCHO条件的反应不同。与H460和MC-38移植物相比,A549肿瘤移植物具有更高的血管密度和更小的肿瘤直径,对HCHO的T1有显著反应,在HC期间T2略有增加,在HCHO下显著增加,这与常氧表型和功能性血管反应性一致。因此,气体激发能够根据肿瘤移植物的血管和氧合状态进行差异表征。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/5d57/9265041/818e4434b431/cancers-14-03114-g001.jpg

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