Melanoma Incidence in Children and Adolescents: Decreasing Trends in the United States.

OBJECTIVE: To assess trends in the incidence of melanoma in children and adolescents in the US from 2000-2010. STUDY DESIGN: Using the Surveillance, Epidemiology, and End Results cancer registry data, we calculated age-adjusted incidence rates of melanoma in children and adolescents (age <20 years) from 2000-2010, as well as annual percent changes. We analyzed incidence trends using joinpoint regression models. We further stratified incidence rates and trends by age group, sex, race, and melanoma-specific characteristic (histology, anatomic site, Breslow depth, ulceration status, lymph node involvement, and presence of metastasis). RESULTS: We included 1185 pediatric patients (age <20 years) diagnosed with melanoma from 2000-2010. In patients age <20 years overall, we found a significant decreasing incidence (11.58% per year) from 2004-2010. Overall, significant decreasing incidence trends were also noted in males, melanoma located on the trunk, melanoma located on the upper extremities, superficial spreading melanoma, and melanoma with good prognostic indicators. When further subdividing the pediatric population by age group, these significant decreasing incidence trends were most notable in adolescents (age 15-19 years), decreasing 11.08% per year from 2003-2010. Furthermore, in 15- to 19-year-olds, decreasing trends were found to be significant in melanoma located on the trunk, superficial spreading melanoma, and melanoma with good prognostic indicators. CONCLUSIONS: Decreasing trends in melanoma incidence in the pediatric population from 2000-2010 stand in contrast to previous reports of increasing long-term incidence trends. Possible contributors to these decreasing trends include effective public health initiatives, decreased time spent outdoors, and increased sunscreen use.

Neighbor effects of neurons bearing protective transgenes.

Viral vectors bearing protective transgenes can decrease neurotoxicity after varied necrotic insults. A neuron that dies necrotically releases glutamate, calcium and reactive oxygen species, thereby potentially damaging neighboring neurons. This raises the possibility that preventing such neuron death via gene therapy can secondarily protect neighboring neurons that, themselves, do not express a protective transgene. We determined whether such "good neighbor" effects occur, by characterizing neurons that, while uninfected themselves, are in close proximity to a transgene-bearing neuron. We tested two genes whose overexpression protects against excitotoxicity: anti-apoptotic Bcl-2, and a calcium-activated K(+) channel, SK2. Using herpes simplex virus type 2-mediated transgene delivery to hippocampal cultures, we observed "good neighbor" effects on neuronal survival following an excitotoxic insult. However, in the absence of insult, "bad neighbor" effects could also occur (i.e., where being in proximity to a neuron constitutively expressing one of those transgenes is deleterious). We also characterized the necessity for cell-cell contact for these effects. These phenomena may have broad implications for the efficacy of gene overexpression strategies in the CNS.