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- Fumagalli, G., et al.
(author)
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Assessment of Neurofilament Light Protein as a Serum Biomarker in Rodent Models of Toxic-Induced Peripheral Neuropathy
- 2021
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In: Experimental Neurotoxicology Methods. Llorens J., Barenys M. (eds). - New York, NY : Springer. - 0893-2336. - 9781071616376 ; , s. 267-275
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Book chapter (other academic/artistic)abstract
- Chemotherapy-Induced Peripheral Neurotoxicity (CIPN) is a side effect frequently caused by common antitumor drugs, which may induce a severe and persistent limitation of the quality of life of cancer patients. Today, nerve conduction studies are considered the most objective indicators for CIPN diagnosis. Unfortunately, they are not easily available at most oncology centers. Therefore, a noninvasive and highly sensitive method is required to confirm nerve damage. Increased evidence supports the potential utility of fluid-based biomarkers to predict tissue damage and to monitor neurotoxicity due to drug administration or the efficacy of disease-modifying treatments. Neurofilaments, the major intermediate filaments in neurons that are specifically expressed in axons, have been investigated as potential biomarker candidates that might be used for this purpose. Neurofilament light chain (NfL) protein is increasingly proposed as a blood biomarker in several neurological diseases mainly affecting the central nervous system. In addition, analysis of serum NfL was evaluated also in peripheral neuropathies including Guillain–Barré syndrome, chronic inflammatory demyelinating and vasculitic neuropathies, and Charcot–Marie–Tooth. This chapter aims to provide an overview of the methods that allow NfL quantification in serum, focusing on the most recent ultrasensitive single molecule array (Simoa) assay. This technique is likely to be the best method for NfL dosage in CIPN models to predict the onset of large caliber neuronal dysfunction. Since blood sampling is an easily accessible technique, serum NfL may provide important help to monitor neuroaxonal damage after chemotherapy treatment, and might represent promising tools to follow CIPN progress. © 2021, Springer Science+Business Media, LLC, part of Springer Nature.
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- Meregalli, C., et al.
(author)
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Neurofilament light chain: a specific serum biomarker of axonal damage severity in rat models of Chemotherapy-Induced Peripheral Neurotoxicity
- 2020
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In: Archives of Toxicology. - : Springer Science and Business Media LLC. - 0340-5761 .- 1432-0738. ; 94, s. 2517-2522
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Journal article (peer-reviewed)abstract
- Chemotherapy-Induced Peripheral Neurotoxicity (CIPN) is a severe and long-lasting side effect of anticancer therapy, which can severely impair patients' quality of life. It is a sensory and length-dependent neuropathy, which predominantly affects large myelinated fibers. Easy and reliable monitoring of CIPN in patients is still an unmet clinical need. Since increasing clinical evidence supports the potential use of neurofilament light chain (NfL) as a biomarker of axonal injury, in this study we measured serum NfL levels in animals chronically treated with cisplatin (CDDP) and paclitaxel (PTX), two antineoplastic drugs with different neuronal targets. Wistar rats were treated with CDDP (2 mg/kg i.p. twice/week for 4 weeks) or PTX (10 mg/kg i.v. once/week for 4 weeks). Repeated serum NfL quantification was obtained using the Single Molecule Array (Simoa) technology. The onset and progression of peripheral neurotoxicity were evaluated through neurophysiology, morphological assessments and intraepidermal nerve fibers density quantification. Our results showed that serum NfL measurements correlated with the severity of axonal damage. In fact, both treatments induced serum NfL increase, but higher levels were evidenced in PTX-treated animals, compared with CDDP-treated rats, affected by a milder neurotoxicity. Notably, also the timing of the NfL level increase was associated with the severity of morphological and functional alterations of axonal structure. Therefore, NfL could be a useful biomarker for axonal damage in order to follow the onset and severity of axonal degeneration and possibly limit the occurrence of serious PNS disease.
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- Meregalli, C., et al.
(author)
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Neurofilament light chain as disease biomarker in a rodent model of chemotherapy induced peripheral neuropathy
- 2018
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In: Experimental Neurology. - : Elsevier BV. - 0014-4886. ; 307, s. 129-132
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Journal article (peer-reviewed)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.
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