| 1. |
- Meregalli, C., et al.
(författare)
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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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Ingår i: Archives of Toxicology. - : Springer Science and Business Media LLC. - 0340-5761 .- 1432-0738. ; 94, s. 2517-2522
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Tidskriftsartikel (refereegranskat)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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| 2. |
- Meregalli, C., et al.
(författare)
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Neurofilament light chain as disease biomarker in a rodent model of chemotherapy induced peripheral neuropathy
- 2018
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Ingår i: Experimental Neurology. - : Elsevier BV. - 0014-4886. ; 307, s. 129-132
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Tidskriftsartikel (refereegranskat)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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| 3. |
- Perfecto-Avalos, Yocanxóchitl, et al.
(författare)
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Denaturing high-performance liquid chromatography and principal component analysis for identification of DNA point mutations in breast cancer and lymphoma samples
- 2018
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Ingår i: Journal of Chemometrics. - : Wiley. - 0886-9383. ; 32:10
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Tidskriftsartikel (refereegranskat)abstract
- Abstract DNA mutations are identified by techniques that use the knowledge of the wild-type DNA sequence and its mutated variant. The involved analytic methods must be accurate, rapid, and sustainable, if a clinical application is pursued. High-performance liquid chromatography under denaturing conditions is a useful technique to screen mutations. Denaturing high-performance liquid chromatography resultant chromatograms are suitable for feature extraction analysis with multivariate methods such as principal component analysis. In this work, principal component analysis was applied to analyze the chromatograms from 3 different genes. Fragments with verified wild-type sequence were used as reference and samples with sequence unknown were tested. A statistical characterization based on Tukey’s boxplot equation of principal component scores allowed us to analyze the distance distribution between reference and sample clusters to establish a classification criterion: an outlier could represent a mutated sample, and a typical value could be a wild-type sample. Identified outliers were further analyzed by sequencing and proved to carry a mutation. From 72 datasets with a total of 4258 injections, we successfully assessed the classification criterion, identifying mutated samples in lymphoma and breast cancer patients with ratio of prediction Gmean = [0.89, 1.00]. Compared with sequencing analysis, this procedure reduced time and costs.
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| 4. |
- Zanon, M., et al.
(författare)
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Microwave-assisted methacrylation of chitosan for 3D printable hydrogels in tissue engineering
- 2022
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Ingår i: Materials Advances. - : Royal Society of Chemistry (RSC). - 2633-5409. ; 3:1, s. 514-525
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Tidskriftsartikel (refereegranskat)abstract
- Light processable natural polymers are highly attractive for 3D printing of biomedical hydrogels with defined geometries and sizes. However, functionalization with photo-curable groups, such as methacrylate or acrylate groups, is required. Here, we investigated a microwave-assisted process for methacrylation of chitosan to replace conventional methacrylation processes that can be time consuming and tedious. The microwave-assisted methacrylation reaction was optimized by varying the synthesis parameters such as the molar ratio of chitosan to the methacrylic agent, the launch and reaction times and process temperature. The optimized process was fast and efficient and allowed tuning of the degree of substitution and thereby the final hydrogel properties. The successful methacrylation and degree of substitution were verified by 1H NMR and attenuated total reflectance-Fourier transform infrared spectroscopy (ATR-FTIR). The influence of the degree of methacrylation on photo-rheology, mechanical stiffness, swelling degree and gel content was evaluated. Furthermore, favourable 3D printability, enzymatic degradability, biocompatibility, cell migration and proliferation were demonstrated giving promise for further applications in tissue engineering.
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