Healing Potential of Propolis Extract-Passiflora edulis Seed Oil Emulgel Against Excisional Wound: Biochemical, Histopathological, and Cytokines Level Evidence.

Propolis is rich in natural bioactive compounds, and considering its importance for many skin therapies, emulgel was prepared. This study examines how a propolis extract (PE) and Passiflora edulis seed (PS) oil emulgel affect rat deep skin wound healing. Based on preset criteria of maximum drug content and optimum drug permeation through the stratum corneum along with drug retention in the skin layers, an optimized emulgel formula based on Box-Behnken factorial design was prepared and used for subsequent in vitro and in vivo evaluations. In vivo wound-healing activities of emulgel and control treatments were investigated in a rat model. The optimized emulgel formula exhibited superior healing activity compared with plain PE suspension-treated rats on day 14 of wounding. Histopathological investigations of hematoxylin and eosin and Masson's Trichrome-stained skin sections supported this effect. Emulgel promotes cutaneous wound healing through a variety of mechanisms, including anti-inflammatory through modulation of cytokines tumor necrosis factor-α, interleukin (IL)-1ß, and IL-6 production, and promotion of collagen fiber formation, all of which contribute to tissue remodeling. Furthermore, when compared with propolis suspension, emulgel showed significant antioxidant and anti-inflammatory effects. Emulgel significantly increased the skin's hydroxyproline level, antioxidant potential, wound contraction, increased penetration, and localized propolis deposition across the skin. Incorporation of PS oil into the emulgel accelerates the tissue regeneration process. The findings suggest that 5% propolis emulgel could be used as an alternative to treat wounds.

Cabozantinib in Patients with Advanced Merkel Cell Carcinoma.

BACKGROUND: This study sought to determine the efficacy and safety profile of cabozantinib in patients with advanced Merkel cell carcinoma (MCC). EXPERIMENTAL DESIGN: This prospective, phase II, single-institution trial enrolled patients with platinum-failure, recurrent/metastatic MCC to receive cabozantinib 60 mg orally daily until disease progression, withdrawal from study, or severe toxicity. The primary endpoint was disease control rate. Secondary endpoints included overall survival (OS), progression-free survival (PFS), and toxicity. Immunohistochemistry for VEGFR-2, MET, and HGF expression and next-generation sequencing of tumor tissue were performed and correlated with outcome. RESULTS: Eight patients were accrued from January 24, 2014, to June 8, 2016. The study was closed prematurely because of toxicity and lack of responses. The most frequent adverse events were grades 1 and 2 and included anorexia, fatigue, nausea, hypothyroidism, and dysgeusia. Two patients developed nonhealing, painful ulcers and tumor-skin fistula. One patient had stable disease for 8 months. One patient withdrew from the study after 2 weeks of therapy because of adverse events. Three patients required dose reduction because of toxicity. Median PFS and OS were 2.1 and 11.2 months, respectively. No expression of MET, HGF, or VEGFR-2 was identified in tumor cells by immunohistochemistry of patients' tissue samples. CONCLUSION: Cabozantinib was poorly tolerated and did not demonstrate activity in patients with recurrent/metastatic, platinum-failure MCC. It is unclear whether preselection of patients with the specific upregulation or genetic alteration in the targets for cabozantinib would have changed the results of this study. (Clinical trial identification number: NCT02036476) IMPLICATIONS FOR PRACTICE: This phase II study demonstrated poor tolerability and lack of activity of cabozantinib in an unselected group of patients with advanced Merkel cell carcinoma. Although it is unclear whether preselection of patients with the specific upregulation and genetic alterations in targets for cabozantinib would have changed the results of this study, this would have likely led to an extremely rare patient population that would take many years to accrue.