The role of Epstein–Barr virus (EBV) infection in the development and progression of tumor cells has been described in various cancers. Etiologically, EBV is a causative agent in certain variants of head and neck cancers such as nasopharyngeal cancer. Proteins expressed by the EVB genome are involved in invoking and perpetuating the oncogenic properties of the virus. However, these protein products were also identified as important targets for therapeutic research in the past decades, particularly within the context of immunotherapy. The adoptive transfer of EBV-targeted T-cells as well as the development of EBV vaccines has opened newer lines of research to conceptualize novel therapeutic approaches toward the disease. This review addresses the most important aspects of the association of EBV with head and neck cancers from an immunological perspective. It also aims to highlight the current and future prospects of enhanced EBV-targeted immunotherapies.
Harpagophytum procumbens, commonly known as Devil's Claw, is indigenous to southern Africa, and extracts of the tubers have been used for centuries in the treatment of a variety of inflammatory disorders. Its major active components, harpagoside (1), harpagide (2), 8-coumaroylharpagide (3), and verbascoside (4), are believed to interact either synergistically or antagonistically in modulating the enzymes responsible for inducing inflammation, although this has not been probed hitherto. In the current work, the ability of these compounds to inhibit the expression of COX-2 following administration to freshly excised porcine skin has been investigated. An ethanol-soluble extract of H. procumbens tubers and two of the pure compounds tested showed promising activity in Western blotting and immunocytochemical assays, with harpagoside (1) and 8-coumaroylharpagide (3) exhibiting greater reductions in COX-2 expression than verbascoside (4). Harpagide (2) caused a significant increase in the levels of COX-2 expression after 6 h of topical application. The data suggest that the efficacy of H. procumbens is dependent upon the ratios of compounds 1-4 present, which is inconsistent with some current official monograph specifications based solely on harpagoside (1) content.
Fish oil enhanced the delivery of BD and SA across skin. Addition of fish oil also enhanced the anti-inflammatory activity of BD, attributed to increased amounts of BD present in the skin and/or the intrinsic anti-inflammatory activity of fish oil.
The potential of the administration of Harpagophytum procumbens extract via the topical route has not been studied previously. In the current work, the dermal and transcutaneous delivery of the major pharmacologically active constituents present in H. procumbens tuber extract were determined across porcine ear skin from four vehicles: de-ionised water, 30 % ethanol in water (v/v), PEG 400, 50 : 50 PEG 400 in 30 % EtOH (v/v). Permeation profiles were obtained under infinite conditions and tape stripping was performed at 24 h. The permeation of the compounds varied according to their physicochemical properties as well as the nature of the vehicle. The highest permeation was found from the ethanol/water saturated solutions and the lowest MW harpagide was obtained at significantly higher concentrations in the receptor phase compared to the rest of the compounds, with the permeability coefficient being inversely dependent on dielectric constant of the vehicle. Depth profiling revealed higher penetration of all compounds from ethanol/water; in addition, significantly higher amounts of the pro-inflammatory harpagide were present in the strips and the remaining epidermis compared to other compounds. This suggests that ethanol is not a suitable vehicle as it leads to more harpagide penetration, potentially counteracting the anti-inflammatory activity of the other compounds. The development of new systems for local cutaneous inflammation (e. g., psoriasis, eczema) and subcutaneous inflammation (e. g., arthritis) is supported.
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