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基于生物物理 profiling 方法研究的糖基化相关变化,探讨晚期黑色素瘤的新型诊断和预后因素。

Novel diagnostic and prognostic factors for the advanced melanoma based on the glycosylation-related changes studied by biophysical profiling methods.

机构信息

Faculty of Chemistry, Warsaw University of Technology, Warsaw, Poland.

Faculty of Chemistry, Warsaw University of Technology, Warsaw, Poland; Polish Stem Cell Bank, Warsaw, Poland.

出版信息

Biosens Bioelectron. 2022 May 1;203:114046. doi: 10.1016/j.bios.2022.114046. Epub 2022 Jan 29.

Abstract

Melanoma is a life-threatening disease due to the early onset of metastasis and frequent resistance to the applied treatment. For now, no single histological, immunohistochemical or serological biomarker was able to provide a precise predictive value for the aggressive behavior in melanoma patients. Thus, the search for quantifying methods allowing a simultaneous diagnosis and prognosis of melanoma patients is highly desirable. By investigating specific molecular interactions with some biosensor-based techniques, one can determine novel prognostic factors for this tumor. In our previous study, we have shown the possibility of a qualitative in vitro distinguishing the commercially available melanoma cells at different progression stages based on the measurements of the lectin Concanavalin A interacting with surface glycans present on cells. Here, we present the results of the quantitative diagnostic and prognostic study of both commercial and patient-derived melanoma cells based on the evaluation of two novel factors: lectin affinity and glycan viscoelastic index obtained from the quartz crystal microbalance with dissipation monitoring (QCM-D) measurements. Two approaches to the QCM-D measurements were applied, the first uses the ability of melanoma cells to grow as a monolayer of cells on the sensor (cell-based sensors), and the second shortens the time of the analysis (suspension cell based-sensors). The results were confirmed by the complementary label-free (atomic force microscopy, AFM; and surface plasmon resonance, SPR) and labeling (lectin-ELISA; and microscale thermophoresis, MST) techniques. This new approach provides additional quantitative diagnosis and a personalized prognosis which can be done simultaneously to the traditional histopathological analysis.

摘要

黑色素瘤是一种危及生命的疾病,因为它早期发生转移,并且经常对应用的治疗产生耐药性。目前,没有单一的组织学、免疫组织化学或血清学生物标志物能够为黑色素瘤患者的侵袭性行为提供准确的预测价值。因此,寻找能够同时诊断和预测黑色素瘤患者的定量方法是非常需要的。通过研究与一些基于生物传感器的技术的特定分子相互作用,可以确定这种肿瘤的新的预后因素。在我们之前的研究中,我们已经表明了基于细胞表面糖链与凝集素 Concanavalin A 相互作用的测量,在体外定性区分不同进展阶段的商业黑色素瘤细胞的可能性。在这里,我们根据从石英晶体微天平耗散监测(QCM-D)测量中获得的两种新型因子:凝集素亲和力和聚糖粘弹性指数,介绍了商业和患者来源的黑色素瘤细胞的定量诊断和预后研究的结果。应用了两种 QCM-D 测量方法,第一种方法利用黑色素瘤细胞在传感器上生长为单层细胞的能力(基于细胞的传感器),第二种方法缩短了分析时间(悬浮细胞基于传感器)。通过互补的无标记(原子力显微镜(AFM)和表面等离子体共振(SPR))和标记(凝集素 ELISA 和微尺度热泳(MST))技术证实了这些结果。这种新方法提供了额外的定量诊断和个性化预后,可以与传统的组织病理学分析同时进行。

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