Silicon phthalocyanine (Pc 4) photodynamic therapy is a safe modality for cutaneous neoplasms: results of a phase 1 clinical trial.

BACKGROUND: Photodynamic therapy (PDT) is a non-invasive treatment for non-melanoma skin cancer. However, PDT systems currently used clinically have limitations such as pain and superficial tissue penetration. The silicon phthalocyanine Pc 4 is a second-generation photosensitizer with peak absorption in the far red at 675 nm. OBJECTIVE: To assess the safety and tolerability of topically applied Pc 4 followed by red light (Pc 4-PDT) in treating cutaneous neoplasms. STUDY DESIGN/MATERIALS AND METHODS: Forty three adults with a diagnosis of neoplasms including actinic keratoses, Bowen's disease, squamous cell carcinoma, basal cell carcinoma, or mycosis fungoides were treated with a single administration of Pc 4-PDT and followed for 14 days. The study utilized a light and Pc 4 dose escalation design in sequential groups of three subjects each. RESULTS: Pc 4-PDT was well tolerated with no significant local toxicity or increased photosensitivity. It has promising biologic effects, particularly in mycosis fungoides where 14 of 35 subjects demonstrated a clinical response, which correlates with Pc 4-PDT-induced apoptosis, as measured by increased active caspase-3 in the treated skin lesions. CONCLUSIONS: Pc 4-PDT is a safe and tolerable treatment modality that effectively triggers apoptosis in cutaneous neoplasms such as mycosis fungoides.

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.

Smoking and skin aging in identical twins.

BACKGROUND: A twin pair can provide a rare opportunity to control for genetic susceptibility and exposure variables, which often serve as major confounders in population-based studies on the relationship between smoking and skin aging. OBSERVATIONS: We describe a unique twin pair who spent not only their first 2 decades of life together but also in their later decades had the same type of job at the same latitude, resulting in well-matched levels of significant sun exposure. However, the twins differed markedly in regard to smoking history; the twin with an approximately 52.5-pack-year smoking history showed more severe skin aging than did the nonsmoking twin. CONCLUSION: The difference in skin aging illustrated by this twin pair may serve as a motivator for smoking cessation.

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.

Ultraviolet immunosuppression: mechanisms and consequences.

It is well recognized that exposure to solar radiation has several detrimental consequences, both acute and chronic. The suppression of immune functions remains one of the most intriguing phenomena brought about by ultraviolet (UV) radiation. This concept has challenged experts from various disciplines including dermatology, immunology, and photobiology. Although controversies exist regarding the mechanisms involved, the consensus is that UV immune suppression contributes significantly to the growth of cutaneous malignancies--both melanoma and nonmelanoma skin cancer. It is therefore a critical issue to be addressed in the context of developing and using sun protection strategies.

Protective effects of tea polyphenols and caffeine.

Compounds derived from botanical sources, such as polyphenols from tea, have been of interest as possible therapeutic agents. Their benefits in terms of cancer chemoprevention have also been investigated primarily through in vitro and animal in vivo studies. Ultraviolet light from solar radiation has been proven to initiate and promote skin cancer, which is the most common malignancy in light-skinned populations. This review discusses the effects of tea polyphenols in preventing cutaneous carcinogenesis. Although many of the mechanisms and pathways discussed may be applicable to other carcinogens, this review focuses mainly on those related to ultraviolet light-induced processes and potential action sites for tea polyphenols. Since caffeine is a component of tea, and has also been suggested as a possible chemoprotective agent, it is included in this review. Based on data from numerous studies published in the scientific literature, tea polyphenols are promising chemopreventive agents against ultraviolet-induced skin cancers. Their antioxidant properties, inhibitory effects on signal transduction pathways, cell proliferation, angiogenesis and capacity for apoptosis induction, as well as possible immune protective effects, are among the mechanisms that contribute to skin cancer prevention.