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神经丝轻链作为化疗诱导周围神经病的啮齿动物模型中的疾病生物标志物。

Neurofilament light chain as disease biomarker in a rodent model of chemotherapy induced peripheral neuropathy.

机构信息

School of Medicine and Surgery, Experimental Neurology Unit and NeuroMI, University of Milano-Bicocca, Monza, Italy.

School of Medicine and Surgery, Experimental Neurology Unit and NeuroMI, University of Milano-Bicocca, Monza, Italy; PhD program in Neuroscience, University of Milano-Bicocca, Monza, Italy.

出版信息

Exp Neurol. 2018 Sep;307:129-132. doi: 10.1016/j.expneurol.2018.06.005. Epub 2018 Jun 13.

Abstract

The objective of this study is to test the feasibility of using serum neurofilament light chain (NfL) as a disease biomarker in Chemotherapy Induced Peripheral Neuropathy (CIPN) since this easy accessible biological test may have a large impact on clinical management and safety of cancer patients. We performed this preclinical study using a well-characterized rat model based on repeated administration of the cytostatic drug vincristine (VCR, 0.2 mg/kg intravenously via the tail vein once/week for 4 times). Serial NfL serum concentration was measured using the in-house Simoa NfL assay and peripheral neuropathy onset was measured by sensory and motor nerve conduction studies. Serum NfL measure in untreated and VCR-treated rats demonstrated a steady, and significant increase during the course of VCR administration, with a final 4-fold increase with respect to controls (p < .001) when sign of axonopathy and loss of intraepidermal nerve fibers were clearly evident and verified by behavioral, neurophysiological and pathological examination. This simple monitoring approach based on serum NfL concentration measures may be easily translated to clinical practice and should be considered as a putative marker of CIPN severity in a typical oncology outpatient setting. Further studies are needed to validate its utility in cancer patients treated with different neurotoxic drugs.

摘要

本研究旨在测试血清神经丝轻链(NfL)作为化疗诱导性周围神经病(CIPN)疾病生物标志物的可行性,因为这种易于获取的生物测试可能对癌症患者的临床管理和安全性产生重大影响。我们使用基于反复给予细胞毒性药物长春新碱(VCR,尾静脉静脉内 0.2mg/kg,每周一次,共 4 次)的特征明确的大鼠模型进行了这项临床前研究。使用内部 Simoa NfL 测定法测量血清 NfL 浓度,并通过感觉和运动神经传导研究测量周围神经病的发作。未经处理和 VCR 处理的大鼠的血清 NfL 测量值在 VCR 给药过程中呈稳定且显著增加,与对照组相比,最终增加了 4 倍(p<0.001),当轴突病和表皮内神经纤维丢失的迹象明显时,通过行为、神经生理学和病理学检查得到证实。这种基于血清 NfL 浓度测量的简单监测方法可能很容易转化为临床实践,并且应该被视为典型肿瘤门诊环境中 CIPN 严重程度的潜在标志物。需要进一步的研究来验证其在接受不同神经毒性药物治疗的癌症患者中的效用。

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