Non-sunscreen photoprotection: antioxidants add value to a sunscreen.

The association between ultraviolet radiation (UVR) exposure and both skin cancer and photo-aging is well documented. In addition to the conventional organic-chemical and physical-mineral type sunscreens, other non-sunscreen protective strategies have been developed. These include topically applied botanical extracts and other antioxidants as well as topical DNA repair enzymes. Standard terms of photoprotection such as sun protection factor (SPF) do not accurately reflect the photoprotection benefits of these materials. For example, in spite of minimal SPF, tea extract containing polyphenols such as (-)-epigallocatechin-3-gallate (EGCG) has been shown to protect against UV-induced DNA damage and immune suppression, in part through its ability to reduce oxidative stress and inhibit NF-kB. The addition of botanical antioxidants and vitamins C and E to a broad-spectrum sunscreen may further decrease UV-induced damage compared with sunscreen alone. These agents have been shown to enhance protection against UV-induced epidermal thickening, overexpression of MMP-1and MMP-9, and depletion of CD1a(+) Langerhans cells. Non-sunscreen materials such as botanical extracts, antioxidants, and DNA repair enzymes can contribute value when applied topically to human skin in vivo.Journal of Investigative Dermatology Symposium Proceedings (2009) 14, 56-59; doi:10.1038/jidsymp.2009.14.

Review of extracorporeal photopheresis in early-stage (IA, IB, and IIA) cutaneous T-cell lymphoma.

BACKGROUND: Extracorporeal photopheresis (ECP) has been used for nearly 20 years for the treatment of cutaneous T-cell lymphoma (CTCL). A substantial body of literature reports that this form of photoimmunotherapy improves or stabilizes the course of disease in a subset of patients across all stages. However, current clinical approach usually reserves ECP for patients who do not respond to other treatments or for patients with late-stage disease or Sézary syndrome (SS). METHODS: A comprehensive Pubmed/Medline literature search was performed to identify studies reporting the use and efficacy of ECP in early stage (IA, IB, and IIA) CTCL. Information regarding prognostic factors and survival of early-stage patients treated with ECP was also obtained and summarized. RESULTS: The heterogenous nature of the reports and lack of any prospective randomized trials made evaluation of response to treatment difficult. However, the current literature contains at least 124 early-stage patients treated with ECP or ECP plus adjuvant therapy from 1987-2007 in 16 different reports. Response rates of treatment for this patient population with ECP and ECP plus adjuvant therapy varied from 33-88%. CONCLUSIONS: Given the very low side effect profile of ECP compared with other therapies and its demonstrated efficacy, this treatment modality is possibly beneficial for patients with earlier stages of CTCL. Randomized prospective studies are needed to establish the role of ECP in this disease subset.

Photodynamic therapy with the phthalocyanine photosensitizer Pc 4: the case experience with preclinical mechanistic and early clinical-translational studies.

Photodynamic therapy (PDT) is emerging as a promising non-invasive treatment for cancers. PDT involves either local or systemic administration of a photosensitizing drug, which preferentially localizes within the tumor, followed by illumination of the involved organ with light, usually from a laser source. Here, we provide a selective overview of our experience with PDT at Case Western Reserve University, specifically with the silicon phthalocyanine photosensitizer Pc 4. We first review our in vitro studies evaluating the mechanism of cell killing by Pc 4-PDT. Then we briefly describe our clinical experience in a Phase I trial of Pc 4-PDT and our preliminary translational studies evaluating the mechanisms behind tumor responses. Preclinical work identified (a) cardiolipin and the anti-apoptotic proteins Bcl-2 and Bcl-xL as targets of Pc 4-PDT, (b) the intrinsic pathway of apoptosis, with the key participation of caspase-3, as a central response of many human cancer cells to Pc 4-PDT, (c) signaling pathways that could modify apoptosis, and (d) a formulation by which Pc 4 could be applied topically to human skin and penetrate at least through the basal layer of the epidermis. Clinical-translational studies enabled us to develop an immunohistochemical assay for caspase-3 activation, using biopsies from patients treated with topical Pc 4 in a Phase I PDT trial for cutaneous T-cell lymphoma. Results suggest that this assay may be used as an early biomarker of clinical response.

Effect of topical vitamin D analogue on in vivo contact sensitization.

BACKGROUND: The immunomodulatory role of vitamin D and its analogues has been demonstrated in vitro and in vivo using animal models. We evaluated the effect of a vitamin D analogue, calcipotriene, in vivo on human subjects using a contact hypersensitivity model. OBSERVATIONS: Subjects were pretreated with topical calcipotriene, simulated solar radiation, or both on buttock skin. They were then sensitized and challenged using the contact allergen dinitrochlorobenzene. Immune response was measured by change in skinfold thickness before vs after elicitation across the challenge sites. CONCLUSIONS: Calcipotriene-treated individuals demonstrated 64% immunosuppression compared with untreated controls. This is equivalent to the immunosuppression induced by UV exposure.

Laser-assisted penetration of allergens for patch testing.

BACKGROUND: Patch-test patients often complain of itching and inconvenience. OBJECTIVE: To demonstrate (1) the usefulness of laser-assisted alteration of the stratum corneum to enhance allergen delivery and (2) patient satisfaction with this procedure. METHODS: The LAD-01 (erbium:yttrium-aluminum-garnet) laser unit was used to alter stratum corneum from patients with known sensitivity to nickel or Kathon CG. These allergens were then applied to the laser-pretreated sites for 60 minutes. Results were observed at 24, 48, and 96 hours and at 1 week. One patient who refused conventional patch testing was tested with an entire modified North American standard series tray with the laser patch-test technique. An additional patient with previously demonstrated positive atopy patch-test reactions to environmental organisms was retested with laser pretreatment to the same antigens. RESULTS: Three of three patients known to be sensitive to Kathon CG and eight of eleven known nickel-sensitive patients had positive reactions at the laser-pretreated sites. The patient who was tested with the entire standard series demonstrated relevant positive reactions to formaldehyde and to a textile resin. One subject with known reactions to three environmental organisms reproduced patch-test responses with laser pretreatment. No irritant reactions were noted. Patients reported no pain. CONCLUSION: With further modification, laser pretreatment may improve patient convenience and decrease irritant test reactions owing to occlusion.