A briefing of the latest findings in the literature, including:
At-home Nonablative Fractional Laser Reduces the Appearance of Periorbital Wrinkles
Nonablative fractional laser treatments traditionally are only administered in an office setting by trained professionals. A handheld nonablative fractional laser was investigated for at-home use for treating periorbital wrinkles and was reported to be effective in a study published in the November issue of the Journal of the American Academy of Dermatology.
James Leyden, MD, from the Skin Study Center, Broomall, Pennsylvania, and colleagues conducted a multicenter trial consisting of 2 clinical studies in which 124 participants performed at-home treatment of periorbital wrinkles using a handheld nonablative fractional laser. Both studies comprised an active treatment phase (daily treatments) and a maintenance phase (twice weekly treatments). Ninety participants were followed through completion of the maintenance phase and 36 were followed for up to 5 months after its completion. An in-person investigator assessment, independent blinded review of high-resolution images, and participant self-assessment were used to evaluate treatment.
The researchers found that patients were able to follow written instructions for using the laser with good compliance to the protocol, and treatments were well-tolerated. Independent blinded evaluations showed an improvement in the Fitzpatrick wrinkle scale score by 1 or more grades in 90% of participants at the end of the active phase and in 79% at the end of the maintenance phase. Transient posttreatment erythema was the most prevalent side effect.
“In sum, the test device and at-home treatment regimen was demonstrated to have a favorable safety profile and to be effective at reducing the appearance of periorbital wrinkles,” the authors write. “Subject compliance was high, treatments were well tolerated, and side effects were minimal and transient.”
Source: ©2012 HealthDay, with additional information from the Journal of the American Academy of Dermatology (Leyden J, Stephens TJ, Herndon JH Jr. Multicenter clinical trial of a home-use nonablative fractional laser device for wrinkle reduction [published online ahead of print March 3, 2012]. J Am Acad Dermatol. 2012;67:975-984).
Fractional Versus Ablative Er:YAG Laser for Facial Resurfacing
Laser therapy is one of the most widely utilized tools for skin resurfacing. Multiple sessions of fractional laser treatment with erbium:YAG (Er:YAG) for facial resurfacing are comparable to a single ablative Er:YAG laser treatment, according to a small study published online on October 29 in the Journal of the American Academy of Dermatology.
Moetaz El-Domyati, MD, from Al-Minya University, Cairo, Egypt, and colleagues performed facial resurfacing with single-session ablative Er:YAG laser on 6 patients and fractional Er:YAG laser (4 sessions) on an additional 6 patients. Skin biopsies were assessed histopathologically and immunohistochemically before laser resurfacing and at 1- and 6-month follow-up. Skin biopsy specimens also were quantified for epidermal thickness and neocollagen formation.
The researchers observed increased epidermal thickness with both laser treatments. Increased neocollagen formation was seen in dermal collagen with increased concentration of types I, III, and VII collagen. Studies of dermal elastic tissue showed decreased dermal elastin, while tropoelastin concentrations increased after laser resurfacing. There were no significant differences between the lasers in their clinical effects or on dermal collagen. For the ablative laser, changes in epidermal thickness, elastin, and tropoelastin were substantially more marked.
“Multiple sessions of fractional laser have comparable effects to a single session of ablative Er:YAG laser on dermal collagen but ablative laser has more effect on elastic tissue and epidermis,” the authors write.
Source: ©2012 HealthDay, with additional information from the Journal of the American Academy of Dermatology (El-Domyati M, Abd-El-Raheem T, Abdel-Wahab H, et al. Fractional versus ablative erbium:yttrium-aluminum-garnet laser resurfacing for facial rejuvenation: an objective evaluation [published online ahead of print October 29, 2012]. J Am Acad Dermatol. doi:10.1016/j.jaad.2012.09.014).
Protection From UV Radiation for Melanoma Prevention
Individuals who have pale skin, red hair, and freckles are at highest risk for developing melanoma compared to all other pigmentation types. A study published online on October 31 in Nature concluded that mice with an inactivating mutation in the melanocortin 1 receptor gene, Mc1r, which controls pigment production, have a phenotype similar to red hair and fair skin in humans; these mice have an increased risk for melanoma, even in the absence of UV radiation exposure, which may act by a mechanism of oxidative damage.
Devarati Mitra, from Massachusetts General Hospital, Charlestown, and colleagues used genetically engineered mice carrying an inactivating mutation in the Mc1r gene and introduced a conditional, melanocyte-targeted allele of the most common melanoma oncoprotein, BRAFV600E, to investigate UV radiation–independent carcinogenesis.
The researchers found that without providing additional gene aberrations or UV radiation exposure, there was a high incidence of invasive melanomas in these mice. Following introduction of an albino allele to ablate all pigment production on the Mc1re/e background, selective absence of pheomelanin synthesis was found to be protective against the development of melanoma. Compared with albino Mc1re/e mouse skin, normal Mc1re/e mouse skin was found to have remarkably greater oxidative DNA and lipid damage.
“These data suggest that the pheomelanin pigment pathway produces ultraviolet radiation–independent carcinogenic contributions to melanomagenesis by a mechanism of oxidative damage,” the authors write. “Although protection from ultraviolet radiation remains important, additional strategies may be required for optimal melanoma prevention.”
Source: ©2012 HealthDay, with additional information from Nature (Mitra D, Luo X, Morgan A, et al. An ultraviolet-radiation-independent pathway to melanoma carcinogenesis in the red hair/fair skin background [published online ahead of print October 31, 2012]. Nature. doi:10.1038/nature11624).
RSK Plays Key Role in Melanoma Chemoresistance
Malignant melanoma is a rapidly growing metastatic disease worldwide and there is still no effective therapy for metastatic disease. The mitogen-activated protein kinase (MAPK) p90 ribosomal S6 kinase (RSK) appears to play a role in the poor response of melanoma cells to DNA-damaging agents, according to research published online October 29 in Oncogene.
Hind Ray-David, PhD, from the Université de Montréal, Quebec, Canada, and colleagues studied the ras/MAPK-signaling pathway, which often is deregulated in melanoma.
The researchers found that MAPK-activated protein kinase RSK played a role in melanoma chemoresistance by altering the response to chemotherapeutic agents. In in vivo and in vitro experiments, RSK phosphorylated checkpoint kinase 1 (Chk1) at Ser280, an inhibitory site. RSK was found to be the main protein kinase operating downstream of mitogens and oncogenes of the ras/MAPK pathway, and in melanoma, RSK constitutively phosphorylated Chk1. In response to DNA-damaging agents, RSK inhibition increased Chk1 activity. RSK promoted silencing of the G2 DNA damage checkpoint in a Chk1-dependent manner. Furthermore, RSK inhibitors were found to sensitize melanoma cells to agents that induce DNA damage.
“Together, our results identify a novel link between the ras/MAPK pathway and the DNA damage response, and suggest that RSK inhibitors may be used to modulate chemosensitivity, which is one of the major obstacles to melanoma treatment,” the authors conclude.
Source: ©2012 HealthDay, with additional information from Oncogene (Ray-David H, Romeo Y, Lavoie G, et al. RSK promotes G2 DNA damage checkpoint silencing and participates in melanoma chemoresistance [published online ahead of print October 29, 2012]. Oncogene. doi:10.1038/onc.2012.472).
Using Negative Pigment Network to Distinguish Melanoma From Other Benign Lesions
Negative pigment network (NPN) can be used to distinguish melanoma from Spitz nevus and other benign lesions, according to a study published online on October 11 in the Journal of the American Academy of Dermatology.
Maria A. Pizzichetta, MD, from the National Cancer Institute, Aviano, Italy, and colleagues assessed the frequency, sensitivity, specificity, and odds ratio (OR) of NPN in digitalized images of skin lesions from 679 patients with histopathologic diagnosis of dermatofibroma (115), melanocytic nevus (220), Spitz nevus (139), and melanoma (205).
The researchers found that the frequency of NPN was higher in the melanoma group (34.6%) than in the Spitz nevus (28.8%), melanocytic nevus (18.2%), and dermatofibroma (11.3%) groups. The odds of melanoma diagnosis versus nonmelanoma diagnosis in the presence of NPN increased (OR, 1.8). For melanocytic nevi and dermatofibromas, the OR was very low (0.5 and 0.3, respectively), while for Spitz nevi, the OR of 1.1 was not statistically significant. There was a substantially higher frequency of multicomponent pattern (68.1%), asymmetric pigmentation (92.9%), irregularly distributed NPN (87.3%), and peripheral location of NPN (66.2%) in melanomas compared to dermatofibroma, melanocytic nevus, and Spitz nevus.
Further studies will help to provide dermoscopic and histopathologic correlation of NPN in melanoma and other lesions. “The overall morphologic pattern of NPN, such as the irregular distribution and the peripheral location of NPN, along with the multicomponent pattern and the asymmetric pigmentation could be used as additional features in distinguishing melanoma from Spitz nevus and other benign lesions,” the authors write.
Source: ©2012 HealthDay, with additional information from the Journal of the American Academy of Dermatology (Pizzichetta MA, Talamini R, Marghoob AA, et al. Negative pigment network: an additional dermoscopic feature for the diagnosis of melanoma [published online ahead of print October 11, 2012]. J Am Acad Dermatol. doi:10.1016/j.jaad.2012.08.012).
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