Differential Scanning Calorimetry of Gliomas: A New Tool in Brain Cancer Diagnostics?

Differential Scanning Calorimetry of Gliomas: A New Tool in Brain Cancer Diagnostics?
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DOI:
10.1227/01.neu.0000430296.23799.cd
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发表时间:
2013-08-01
期刊:
影响因子:
4.8
通讯作者:
Jensen, Randy L.
Jensen, Randy L.
中科院分区:
医学1区
文献类型:
--
作者:
Chagovetz, Alexis A.;Quinn, Colette;Jensen, Randy L.

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背景:生物流体中复杂分子相互作用的热稳定性特征可以用差示扫描量热法(DSC)来测量。评估血浆蛋白质组的热稳定性提供了一种在肿瘤和自身免疫性疾病中产生疾病特异性“特征”(热图)的方法。目的:作者描述了使用DSC与人脑肿瘤组织创建与组织学肿瘤分类相关的独特热图。方法:按照世界卫生组织的分类方法对原发性脑肿瘤进行分类。肿瘤样品消化后用DSC量热计测定。实验热图被背景减去并归一化为过渡的总面积,以排除浓度的影响。所得的热图通过应用二态,缩放,高斯分布进行分析。结果:胶质瘤特异性特征的差异是通过在过渡中使用计算参数来描述的,在平衡近似中,通过熔化温度(T-m),表观焓变(δ H)和与过渡中变性材料的相对丰度相关的比例因子(a (w))来表征。多形性胶质母细胞瘤和低级别星形胶质细胞瘤的热成像特征采用A(w3)和T-m4的计算值进行区分,多形性胶质母细胞瘤和少突胶质细胞瘤的热成像特征采用A(w2)、Delta H-2、Delta H-4和T-m4进行区分,低级别星形细胞瘤和少突胶质细胞瘤的热成像特征采用A(w4)进行区分。结论:我们的初步结果表明,实体脑瘤表现出特定的热成像特征,在胶质瘤等级中是可区分的。我们预计我们的结果将形成一种基于组织热像图的新型诊断分析的概念基础,作为目前使用的组织学分析的补充。
BACKGROUND: Thermal stability signatures of complex molecular interactions in biological fluids can be measured using differential scanning calorimetry (DSC). Evaluating the thermal stability of plasma proteomes offers a method of producing a disease-specific "signature" (thermogram) in neoplastic and autoimmune diseases.OBJECTIVE: The authors describe the use of DSC with human brain tumor tissue to create unique thermograms for correlation with histological tumor classification.METHODS: Primary brain tumors were classified according to the World Health Organization classification. Tumor samples were digested and assayed by a DSC calorimeter. Experimental thermograms were background subtracted and normalized to the total area of transitions to exclude concentration effects. The resulting thermograms were analyzed by applying 2-state, scaled, Gaussian distributions.RESULTS: Differences in glioma-specific signatures are described by using calculated parameters at transitions that are characterized, in the equilibrium approximation, by a melting temperature (T-m), an apparent enthalpy change (Delta H), and a scaling factor related to the relative abundance of the materials denatured in the transition (A(w)). Thermogram signatures of glioblastoma multiforme and low-grade astrocytomas were differentiated by calculated values of A(w3) and T-m4, those of glioblastoma multiforme and oligodendrogliomas were differentiated by A(w2), Delta H-2, Delta H-4, and T-m4, and those of low-grade astrocytomas and oligodendroglioma were differentiated by A(w4).CONCLUSION: Our preliminary results suggest that solid brain tumors exhibit specific thermogram profiles that are distinguishable among glioma grades. We anticipate that our results will form the conceptual base of a novel diagnostic assay based on tissue thermograms as a complement to currently used histological analysis.