Lorraine C. Young

Nutrition: The future of melanoma prevention?

BACKGROUND Melanoma is one of the deadliest forms of skin cancer, having a high metastatic potential and afflicting all age groups. The need for successful preventative measures is particularly urgent as metastatic melanoma is largely incurable. The beneficial role of nutrition and other natural compounds in the prevention and treatment of melanoma has been clearly demonstrated in the past, and is an exciting source for potential therapies in the future. OBJECTIVE We sought to review updates in the current literature regarding new developments in the relationship between nutrition and melanoma risk and treatment. METHODS Articles in the public domain regarding the impact of diet, grape seed proanthocyanidins, selenium, vitamin D, vitamin E, epigallocatechin-3-gallate, resveratrol, rosmarinic acid, lycopene, and fig latex on melanoma were included. RESULTS Grape seed proanthocyanidins, epigallocatechin-3-gallate, resveratrol, rosmarinic acid, lycopene, and fig latex have demonstrated clear anticancer effects toward melanoma. The roles of selenium, vitamin D, and vitamin E, however, have been more controversial. LIMITATIONS None. CONCLUSIONS The role of natural compounds in the future of melanoma prevention and treatment is promising and one that is worthy of further exploration.

Palmoplantar Keratoderma along with Neuromuscular and Metabolic Phenotypes in Slurp1-Deficient Mice

Mutations in SLURP1 cause mal de Meleda, a rare palmoplantar keratoderma (PPK). SLURP1 is a secreted protein that is expressed highly in keratinocytes but has also been identified elsewhere (e.g., spinal cord neurons). Here, we examined Slurp1-deficient mice (Slurp1−/−) created by replacing exon 2 with β-gal and neo cassettes. Slurp1−/− mice developed severe PPK characterized by increased keratinocyte proliferation, an accumulation of lipid droplets in the stratum corneum, and a water barrier defect. In addition, Slurp1−/− mice exhibited reduced adiposity, protection from obesity on a high-fat diet, low plasma lipid levels, and a neuromuscular abnormality (hind limb clasping). Initially, it was unclear whether the metabolic and neuromuscular phenotypes were due to Slurp1 deficiency because we found that the targeted Slurp1 mutation reduced the expression of several neighboring genes (e.g., Slurp2, Lypd2). We therefore created a new line of knockout mice (Slurp1X−/− mice) with a simple nonsense mutation in exon 2. The Slurp1X mutation did not reduce the expression of adjacent genes, but Slurp1X−/− mice exhibited all of the phenotypes observed in the original line of knockout mice. Thus, Slurp1 deficiency in mice elicits metabolic and neuromuscular abnormalities in addition to PPK.

Palmoplantar Keratoderma in Slurp2-Deficient Mice

SLURP1, a member of the Ly6 protein family, is secreted by suprabasal keratinocytes. Mutations in SLURP1 cause a palmoplantar keratoderma (PPK) known as mal de Meleda. Another secreted Ly6 protein, SLURP2, is encoded by a gene located ~20 kb downstream from SLURP1. SLURP2 is produced by suprabasal keratinocytes. To investigate the importance of SLURP2, we first examined Slurp2 knockout mice in which exon 2–3 sequences had been replaced with lacZ and neo cassettes. Slurp2−/− mice exhibited hyperkeratosis on the volar surface of the paws (i.e., PPK), increased keratinocyte proliferation, and an accumulation of lipid droplets in the stratum corneum. They also exhibited reduced body weight and hind limb clasping. These phenotypes are very similar to those of Slurp1−/− mice. To solidify a link between Slurp2 deficiency and PPK and to be confident that the disease phenotypes in Slurp2−/− mice were not secondary to the effects of the lacZ and neo cassettes on Slurp1 expression, we created a new line of Slurp2 knockout mice (Slurp2X−/−) in which Slurp2 was inactivated with a simple nonsense mutation. Slurp2X−/− mice exhibited the same disease phenotypes. Thus, Slurp2 deficiency and Slurp1 deficiencies cause the same disease phenotypes.

Aspirin use and melanoma risk: A review of the literature

In view of the increasing incidence of melanoma, it is critical to find effective preventive approaches. Contradictory evidence has been reported with regard to the possible association of aspirin use and the risk of melanoma. We review these studies and seek to elucidate the mechanism by which aspirin may produce a chemoprotective effect against melanoma.

Localized bullous fixed drug eruption following yellow fever vaccine

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A hypomorphic Egfr allele does not ameliorate the palmoplantar keratoderma caused by SLURP1 deficiency

Mutations in SLURP1, a secreted protein of keratinocytes, cause a palmoplantar keratoderma (PPK) known as mal de Meleda. Slurp1 deficiency in mice faithfully recapitulates the human disease, with increased keratinocyte proliferation and thickening of the epidermis on the volar surface of the paws. There has long been speculation that SLURP1 serves as a ligand for a receptor that regulates keratinocyte growth and differentiation. We were intrigued that mutations leading to increased signalling through the epidermal growth factor receptor (EGFR) cause PPK. Here, we sought to determine whether reducing EGFR signalling would ameliorate the PPK associated with SLURP1 deficiency. To address this issue, we bred Slurp1‐deficient mice that were homozygous for a hypomorphic Egfr allele. The hypomorphic Egfr allele, which leads to reduced EGFR signalling in keratinocytes, did not ameliorate the PPK elicited by SLURP1 deficiency, suggesting that SLURP1 deficiency causes PPK independently (or downstream) from the EGFR pathway.

Aspirin use and melanoma: A UCLA pilot study

Study limitations included small convenience samples recruited from a single university that had allowed students to use university debit cards at local tanning salons. Although this practice has since been disallowed, the competitive local business environment for IT salons may have resulted in unusually high rates of DCM. The extent to which findings can be extrapolated to other populations and settings remains to be determined.

Palmoplantar keratoderma in Slurp1/Slurp2 double-knockout mice

Mutations in SLURP1, encoding a secreted protein of keratinocytes, cause a palmoplantar keratoderma (PPK) known as mal de Meleda [1]. When the link between SLURP1 mutations and mal de Meleda was uncovered, there was speculation that SLURP1 might be a ligand for a cell-surface receptor of keratinocytes [1]. Also, because the predicted structure of SLURP1 resembled cobra neurotoxins, there was speculation that SLURP1 might influence

Bullous pemphigoid localized in a primarily hemiplegic distribution

BP: bullous pemphigoid BPAG: bullous pemphigoid antigen CVA: cerebrovascular accident INTRODUCTION Bullous pemphigoid (BP) is an autoimmune disease that results in the formation of tense bullae, usually affecting the elderly population. The pathogenesis involves deposition of IgG autoantibodies in basement membrane hemidesmosomes followed by complement activation and subsequent recruitment of inflammatory cells. Clinically, this activity results in the formation of tense subepidermal blisters and urticarial papules and plaques, most commonly affecting flexural areas, the abdomen, and thighs. During the last decade, several observational studies have reported associations between BP and several neurologic disorders, including dementia, Parkinson disease, bipolar disorder, epilepsy, multiple sclerosis, and stroke. We present a case of BP in a patient with a recent cerebrovascular accident (CVA), primarily involving the same side of the body affected by the stroke.