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Chemotherapy-induced neurotoxicity is an increasingly recognized clinical issue in oncology. in vivo confocal microscopy (IVCM) of corneal nerves has been successfully used to diagnose peripheral neuropathies, including diabetic neuropathy. The purpose of this study was to test if the combination of corneal nerve density and morphology assessed by IVCM is useful to monitor the neurotoxic effects of chemotherapy compared to epidermal nerve quantification. Overall, 95 adult patients with different cancer types were recruited from the oncology and hematology departments of the San Raffaele Hospital. Neurological examination, including clinical Total Neuropathy Score, and in vivo corneal confocal microscopy (IVCM), were performed before and after chemotherapy. In a group of 14 patients, skin biopsy was performed at the first and last visit. In the group of 14 patients who underwent both skin biopsy and corneal nerve imaging, clinical worsening (+69%, p = 0.0018) was paralleled by corneal nerve fiber (CNF) density reduction (−22%, p = 0.0457). Clinical Total neuropathy score significantly worsened from the first to the last visit (+62%, p < 0.0001). CNF length was not significantly reduced overall. However, CNF density/tortuosity ratio significantly decreased after therapy. Correlation analysis showed that the CNF density/tortuosity ratio was also correlated with the number of chemotherapy cycles (r = −0.04790, P = 0.0009). Our data confirm that in vivo corneal confocal microscopy is a helpful, non-invasive tool which shows promise for the diagnosis of chemotherapy-induced peripheral neuropathies. IVCM could allow a rapid, reproducible and non-invasive quantification of peripheral nerve pathology in chemotherapy-associated neuropathy.

Background:Leukocyte migration across the blood barrier and into tissues represents a key process in the pathogenesis of inflammatory bowel diseases. The urokinase receptor (urokinase-type plasminogen activator receptor) is a master regulator of leukocyte recruitment. We recently found that cyclization of the urokinase-type plasminogen activator receptor-derived peptide Ser-Arg-Ser-Arg-Tyr [SRSRY] inhibits transendothelial migration of monocytes. Now, we have explored the effects of [SRSRY] administration during experimental colitis.Methods:The effects of [SRSRY] on cytokine profile, cytoskeletal organization, and cell migration were investigated using phorbol-12-myristate acetate-differentiated THP-1 cells exposed to polarizing stimuli. In vivo, [SRSRY] was intraperitoneally administered during dextran sodium sulfate- or 2,4,6-trinitrobenzene sulfonic acid-induced colitis in wild-type or urokinase-type plasminogen activator receptor knockout mice. Levels of pro-inflammatory cytokines and inflammatory monocytes in mucosal infiltrates were assessed by enzyme-linked immunosorbent assay and flow cytometry, respectively.Results:[SRSRY] prevents M0 to M1 transition and migration of M1 polarized macrophages. In vivo, [SRSRY] reduces intestinal inflammation diminishing body weight loss and disease activity index. These beneficial effects are accompanied by a reduction of interleukin 1, interleukin 6, and tumor necrosis factor , an increase of interleukin 10, and an abridged recruitment of inflammatory monocytes to the inflamed tissue.Conclusions:Altogether, these findings indicate that [SRSRY] may be considered as a new drug useful for the pharmacological treatment of chronic inflammatory diseases, such as inflammatory bowel diseases. BACKGROUND: Leukocyte migration across the blood barrier and into tissues represents a key process in the pathogenesis of inflammatory bowel diseases. The urokinase receptor (urokinase-type plasminogen activator receptor) is a master regulator of leukocyte recruitment. We recently found that cyclization of the urokinase-type plasminogen activator receptor-derived peptide Ser-Arg-Ser-Arg-Tyr [SRSRY] inhibits transendothelial migration of monocytes. Now, we have explored the effects of [SRSRY] administration during experimental colitis.METHODS: The effects of [SRSRY] on cytokine profile, cytoskeletal organization, and cell migration were investigated using phorbol-12-myristate acetate-differentiated THP-1 cells exposed to polarizing stimuli. In vivo, [SRSRY] was intraperitoneally administered during dextran sodium sulfate- or 2,4,6-trinitrobenzene sulfonic acid-induced colitis in wild-type or urokinase-type plasminogen activator receptor knockout mice. Levels of pro-inflammatory cytokines and inflammatory monocytes in mucosal infiltrates were assessed by enzyme-linked immunosorbent assay and flow cytometry, respectively.RESULTS: [SRSRY] prevents M0 to M1 transition and migration of M1 polarized macrophages. In vivo, [SRSRY] reduces intestinal inflammation diminishing body weight loss and disease activity index. These beneficial effects are accompanied by a reduction of interleukin 1β, interleukin 6, and tumor necrosis factor α, an increase of interleukin 10, and an abridged recruitment of inflammatory monocytes to the inflamed tissue.CONCLUSIONS: Altogether, these findings indicate that [SRSRY] may be considered as a new drug useful for the pharmacological treatment of chronic inflammatory diseases, such as inflammatory bowel diseases.