IMPORTANCESkin cancer is the most common malignancy occurring after organ transplantation. Although previous research has reported an increased risk of skin cancer in solid organ transplant recipients (OTRs), no study has estimated the posttransplant population-based incidence in the United States. OBJECTIVE To determine the incidence and evaluate the risk factors for posttransplant skin cancer, including squamous cell carcinoma (SCC), melanoma (MM), and Merkel cell carcinoma (MCC) in a cohort of US OTRs receiving a primary organ transplant in 2003 or 2008. DESIGN, SETTING, AND PARTICIPANTS This multicenter retrospective cohort study examined 10 649 adult recipients of a primary transplant performed at 26 centers across the United States in the Transplant Skin Cancer Network during 1 of 2 calendar years (either 2003 or 2008) identified through the Organ Procurement and Transplantation Network (OPTN) database. Recipients of all organs except intestine were included, and the follow-up periods were 5 and 10 years.MAIN OUTCOMES AND MEASURES Incident skin cancer was determined through detailed medical record review. Data on predictors were obtained from the OPTN database. The incidence rates for posttransplant skin cancer overall and for SCC, MM, and MCC were calculated per 100 000 person-years. Potential risk factors for posttransplant skin cancer were tested using multivariate Cox regression analysis to yield adjusted hazard ratios (HR).RESULTS Overall, 10 649 organ transplant recipients (mean [SD] age, 51 [12] years; 3873 women [36%] and 6776 men [64%]) contributed 59 923 years of follow-up. The incidence rates for posttransplant skin cancer was 1437 per 100 000 person-years. Specific subtype rates for SCC, MM, and MCC were 812, 75, and 2 per 100 000 person-years, respectively. Statistically significant risk factors for posttransplant skin cancer included pretransplant skin cancer (
Cigarette smoking has been associated with significant morbidity affecting all systems of the body, including the integumentary system. We review the many dermatologic hazards of tobacco use. It is important to distinguish between the effects of tobacco smoke from effects of pure nicotine on the skin. All skin cells express several subtypes of the nicotinic class of acetylcholine receptors, including the a7 receptor. Many chronic dermatoses are affected by smoking either negatively or positively. Elucidation of positive associations with a particular disease can lead to improvement from smoking cessation, whereas inverse correlation may lead to development of a disease-specific treatment with nicotinergic agonists.
Background and Objective Pulsed carbon dioxide (CO2) laser devices are considered highly effective treatment options for skin resurfacing. However, the high risk for significant treatment complications following CO2 resurfacing has warranted the development of new treatment modalities. The concept of fractional photothermolysis was developed to address the shortcomings of ablative and non‐ablative device modalities. This report evaluates a fractional approach to CO2 laser resurfacing for the treatment of moderate to severe acne scarring. The primary endpoint of the study was the overall improvement in the appearance of acne scarring. Study Design/Materials and Methods Thirty subjects, with moderate to severe acne scarring, underwent up to three treatments with an FDA IDE and IRB approved 10,600 nm fractional CO2 laser system. All subjects were Fitzpatrick skin types I–V and 18–75 years of age. Treatment parameters ranged from 20 to 100 mJ with total densities of 600–1,600 MTZ/cm2. Improvement of acne scarring was evaluated at 1 and 3 months post‐treatment. Results Twenty‐three out of 25 subjects sustained clinical improvement in the appearance of acne scarring at the 3‐month follow‐up visits according to study investigator quartile improvement scoring. Subjects also had improvement in their overall appearance, including pigmentation and rhytides. Serosanguinous oozing resolved within 24–48 hours following treatment. All subjects had transient erythema, which resolved in the majority of subjects within 1–3 months. Post‐operative downtime was significantly decreased compared to traditional ablative resurfacing. No serious complications were reported. Conclusion Fractional deep dermal ablation improves moderate to severe acne scarring. The added benefit is a considerable reduction both in downtime and risk of complications when compared to traditional CO2 ablative resurfacing techniques. Lasers Surg. Med. 41:122–127, 2009. © 2009 Wiley‐Liss, Inc.
The actin cytoskeleton controls multiple cellular functions, including cell morphology, movement, and growth. Accumulating evidence indicates that oncogenic activation of the mitogen-activated protein kinase kinase/extracellular signal-regulated kinase 1/2 (MEK/ERK1/2) pathway is accompanied by actin cytoskeletal reorganization. However, the signaling events contributing to actin cytoskeleton remodeling mediated by aberrant ERK1/2 activation are largely unknown. Mutant B-RAF is found in a variety of cancers, including melanoma, and it enhances activation of the MEK/ERK1/2 pathway. We show that targeted knockdown of B-RAF with small interfering RNA or pharmacological inhibition of MEK increased actin stress fiber formation and stabilized focal adhesion dynamics in human melanoma cells. These effects were due to stimulation of the Rho/Rho kinase (ROCK)/LIM kinase-2 signaling pathway, cumulating in the inactivation of the actin depolymerizing/severing protein cofilin. The expression of Rnd3, a Rho antagonist, was attenuated after B-RAF knockdown or MEK inhibition, but it was enhanced in melanocytes expressing active B-RAF. Constitutive expression of Rnd3 suppressed the actin cytoskeletal and focal adhesion effects mediated by B-RAF knockdown. Depletion of Rnd3 elevated cofilin phosphorylation and stress fiber formation and reduced cell invasion. Together, our results identify Rnd3 as a regulator of cross talk between the RAF/MEK/ERK and Rho/ROCK signaling pathways, and a key contributor to oncogene-mediated reorganization of the actin cytoskeleton and focal adhesions.
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