Histological basis of MR/optical imaging of human melanoma mouse xenografts spanning a range of metastatic potentials.

Histological basis of MR/optical imaging of human melanoma mouse xenografts spanning a range of metastatic potentials.
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DOI:
10.1007/978-0-387-85998-9_37
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发表时间:
2009
影响因子:
--
通讯作者:
Li LZ
Li LZ
中科院分区:
医学4区
文献类型:
--
作者:
Xu HN;Zhou R;Nioka S;Chance B;Glickson JD;Li LZ

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预测肿瘤的侵袭性将极大地促进癌症治疗。我们之前曾报道过利用各种 MR/光学成像方法来区分跨越一系列转移潜能的人类黑色素瘤小鼠异种移植物的研究。本研究的目的是探讨先前报道的影像学结果的组织学基础。我们获得了三种类型的人黑色素瘤小鼠异种移植物的低温肿瘤切片,其转移潜力的顺序为A375P<A375M<C8161。 H&E和DAPI复染TUNEL分析显示侵袭性肿瘤中明显的核心-边缘差异,而核心明显有许多活细胞形成血管样网络结构,而边缘看起来活细胞密集。攻击性最小的 (A375P) 相对更均匀,没有明显的核心-边缘差异。然而,我们之前的研究表明,更具侵袭性的黑色素瘤的核心具有更高的 Fp/NADH 氧化还原比,表明营养缺乏。此外,之前通过 DCE-MRI 测量的低灌注/血管通透性表明这些细胞应该处于饥饿状态,可能伴随着更多的细胞死亡。因此,更具侵袭性的黑色素瘤核心细胞的生存状态仍然是一个悬而未决的问题。我们目前正在研究这些细胞是否处于自噬状态,这是饥饿条件下可能的细胞生存机制。
Predicting tumor aggressiveness will greatly facilitate cancer treatment. We have previously reported investigations utilizing various MR/optical imaging methods to differentiate human melanoma mouse xenografts spanning a range of metastatic potentials. The purpose of this study was to explore the histological basis of the previously reported imaging findings. We obtained the cryogenic tumor sections of three types of human melanoma mouse xenografts with their metastatic potentials falling in the rank order A375P<A375M<C8161. Both H&E and DAPI counter-stained TUNEL analysis showed distinct core-rim difference in aggressive tumors, while the core has apparently many viable cells forming structure of vascular-like networks and the rim appears viable-cell dense. The least aggressive ones (A375P) are relatively more homogenous without distinct core-rim difference. However, our previous study showed the core of more aggressive melanoma has higher Fp/NADH redox ratio, indicative of nutritional deprivation. Additionally, the low perfusion/blood vessel permeability measured previously by DCE-MRI indicated these cells should be under starvation presumably accompanied with more cell death. Thus, it remains an open question what the survival status of the cells in the core of more aggressive melanoma is. We are currently investigating whether these cells are in autophagic state, a possible cell survival mechanism under starvation conditions.
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