James A. Burch

A topical antioxidant solution containing vitamins C and E stabilized by ferulic acid provides protection for human skin against damage caused by ultraviolet irradiation

BACKGROUND Skin cancer and photoaging changes result from ultraviolet (UV)-induced oxidative stress. Topical antioxidants may protect skin from these effects. OBJECTIVE We sought to determine whether a stable topical formulation of 15% L-ascorbic acid, 1% alpha-tocopherol, and 0.5% ferulic acid (CEFer) could protect human skin in vivo from substantial amounts of solar-simulated UV radiation. METHODS CEFer and its vehicle were applied to separate patches of normal-appearing human skin for 4 days. Each patch was irradiated with solar-simulated UV, 2 to 10 minimal erythema doses, at 2-minimal erythema dose intervals. One day later, skin was evaluated for erythema and sunburn cells, and immunohistochemically for thymine dimers and p53. UV-induced cytokine formation, including interleukin (IL)-1alpha, IL-6, IL-8, and IL-10, and tumor necrosis factor-alpha, were evaluated by real-time polymerase chain reaction. RESULTS CEFer provided significant and meaningful photoprotection for skin by all methods of evaluation. LIMITATIONS The number of patients evaluated was relatively small. CONCLUSION CEFer provided substantial UV photoprotection for skin. It is particularly effective for reducing thymine dimer mutations known to be associated with skin cancer. Its mechanism of action is different from sunscreens and would be expected to supplement the sun protection provided by sunscreens.

Murine dendritic cells transfected with human GP100 elicit both antigen-specific CD8(+) and CD4(+) T-cell responses and are more effective than DNA vaccines at generating anti-tumor immunity.

Dendritic cells (DCs) are potent inducers of cytotoxic T lymphocytes (CTLs) when pulsed with an antigenic peptide or tumor lysate. In this report, we have used liposome‐mediated gene transfer to examine the ability of plasmid DNA encoding the human melanoma‐associated antigen gp100 to elicit CD8+ and CD4+ T‐cell responses. We also compared the efficacy between gp100 gene–modified DCs and naked DNA (pCDNA3/gp100)–based vaccines at inducing anti‐tumor immunity. DCs were generated from murine bone marrow and transfected in vitro with plasmid DNA containing the gp100 gene. These gp100‐modified DCs (DC/gps) were used to stimulate syngeneic naive spleen T cells in vitro or to immunize mice in vivo. Antigen‐specific, MHC‐restricted CTLs were generated when DC/gps were used to prime T cells both in vitro and in vivo. Thus, these CTLs were cytolytic for gp100‐transfected syngeneic (H‐2b) tumor MCA106 (MCA/gp) and vaccinia‐pMel17/gp100‐infected syngeneic B16 and MCA106, but not parental tumor MCA106 and B16, or gp100‐transfected allogeneic tumor P815 (H‐2d). Immunization with DC/gp protected mice from subsequent challenge with MCA/gp but not parental MCA106. Antibody‐mediated T‐cell subset depletion experiments demonstrate that induction of CTLs in vivo is dependent on both CD4+ and CD8+ T cells. Furthermore, DC/gp immunization elicits an antigen‐specific CD4+ T‐cell response, suggesting that DC/gps present MHC class II epitopes to CD4+ T cells. In addition, our data show that gene‐modified, DC‐based vaccines are more effective than the naked DNA‐based vaccines at eliciting anti‐tumor immunity in both prophylactic and therapeutic models. These results suggest that the use of DCs transfected with plasmid DNA containing a gene for TAA may be superior to peptide‐pulsed DCs and naked DNA‐based vaccines for immunotherapy and could provide an alternative strategy for tumor vaccine design. Int. J. Cancer 83:532–540, 1999.

Topical isoflavones provide effective photoprotection to skin

Background/purpose: Isoflavones, one main group of phytoestrogens, have antioxidative and photoprotective effects in cellular and mouse studies. The aim of this study is to obtain a more comprehensive understanding of the isoflavone‐mediated photoprotection with the pig skin model, a more human‐resembling model.

The SCF/KIT pathway plays a critical role in the control of normal human melanocyte homeostasis

During development, the interaction of stem cell factor (SCF) with its receptor, KIT, is critical for the survival of melanocytes. Limited in vivo human studies have suggested a possible activating role of SCF on adult human melanocytes. In order to study the impact of this pathway on normal melanocyte homeostasis, human skin xenografts were treated with serial injections of recombinant human SCF or a KIT-inhibitory antibody (K44.2). On histologic evaluation, SCF injection increased, whereas KIT inhibition decreased the number, size, and dendricity of melanocytes. Immunohistochemical expression of melanocyte differentiation antigens, including tyrosinase-related-protein-1 and gp100/pmel17, was markedly increased by treatment with SCF, and decreased by K44.2 treatment. The number of Ki67-positive melanocytes was increased in the SCF-treated tissue, suggesting a direct proliferative effect of SCF; conversely, treatment with K44.2 resulted in melanocyte loss, which did not appear reversible with prolonged treatment. These findings demonstrate that the SCF/KIT pathway remains critical in adult human skin, and that pharmacologic modulation of this single pathway can control cutaneous melanocyte homeostasis.