New perspectives on the conservative management of osteoradionecrosis of the mandible: A literature review.

Over the last decades, several therapeutic options were considered in the treatment of the osteoradionecrosis (ORN) of the mandible, including supportive measures, ultrasound therapy, corticosteroids, hyperbaric oxygen, surgical resection with reconstruction, and, more recently, drugs capable of reversing the fibroatrophic process. Once established, the ORN does not spontaneously disappear and a standard treatment has not yet been defined. The clear clinical effectiveness of hyperbaric oxygen therapy (HBOT) varies according to the literature and there are some economic/logistic issues to be considered; the triplet tocopherol/pentoxifylline/clodronate demands greater evidence from randomized clinical trials and also resilience from the patient, given the long treatment duration and its possible side effects. Controversy around the ideal treatment of the initial stage ORN of the mandible persists. More rigorous randomized prospective trials are essential. The purpose of this article was to review the relevant literature on the physiopathology of ORN of the mandible and discuss the new perspectives of its conservative treatment. © 2016 Wiley Periodicals, Inc. Head Neck 38: 1708-1716, 2016.

Melanoma expression of matrix metalloproteinase-23 is associated with blunted tumor immunity and poor responses to immunotherapy.

BACKGROUND: Matrix metalloproteinase-23 (MMP-23) can block the voltage-gated potassium channel Kv1.3, whose function is important for sustained Ca(2+) signaling during T cell activation. MMP-23 may also alter T cell activity and phenotype through cleavage of proteins affecting cytokine and chemokine signaling. We therefore tested the hypothesis that MMP-23 can negatively regulate the anti-tumor T cell response in human melanoma. METHODS: We characterized MMP-23 expression in primary melanoma patients who received adjuvant immunotherapy. We examined the association of MMP-23 with the anti-tumor immune response - as assessed by the prevalence of tumor-infiltrating lymphocytes and Foxp3(+) regulatory T cells. Further, we examined the association between MMP-23 expression and response to immunotherapy. Considering also an in trans mechanism, we examined the association of melanoma MMP-23 and melanoma Kv1.3 expression. RESULTS: Our data revealed an inverse association between primary melanoma MMP-23 expression and the anti-tumor T cell response, as demonstrated by decreased tumor-infiltrating lymphocytes (TIL) (P = 0.05), in particular brisk TILs (P = 0.04), and a trend towards an increased proportion of immunosuppressive Foxp3(+) regulatory T cells (P = 0.07). High melanoma MMP-23 expression is also associated with recurrence in patients treated with immune biologics (P = 0.037) but not in those treated with vaccines (P = 0.64). Further, high melanoma MMP-23 expression is associated with shorter periods of progression-free survival for patients receiving immune biologics (P = 0.025). On the other hand, there is no relationship between melanoma MMP-23 and melanoma Kv1.3 expression (P = 0.27). CONCLUSIONS: Our data support a role for MMP-23 as a potential immunosuppressive target in melanoma, as well as a possible biomarker for informing melanoma immunotherapies.