Melanoma incidence and the lifetime risk are increasing at an alarming rate in the United States and worldwide. In order to improve survival rates, the goal is to detect melanoma at an early stage of the disease. Accurate, sensitive and reliable quantitative diagnostic tools can reduce the number of unnecessary biopsies, the associated morbidity as well as the costs of care in addition to improving survival rates. The recently introduced quantitative dynamic infrared imaging system QUAINT measures differences in the infrared emission between healthy tissue and the lesion during the thermal recovery process after the removal of a cooling stress. Results from a clinical study suggest that the temperature of cancerous lesions is higher during the first 45-60 seconds of thermal recovery than the temperature of benign pigmented lesions. This small temperature difference can be measured by modern infrared cameras and serve as an indicator for melanoma in modern quantitative melanoma detectors.

The incidence of melanoma is rising steadily around the world, with varying mortality trends among different populations. Particularly, incidence rates among young adults, below age 40 years, have increased dramatically in the past decades. In young adults, the gender predominance is switched, with the highest incidence occurring in young women. Multiple risk factors are associated with higher risk of developing melanoma. Intermittent sunlight exposure and use of tanning beds early in life increase significantly the risk of melanoma. The prevalence of tanning bed use among young women and adolescents is increasing continuously. This trend may be associated with the increase in melanoma incidence among young women. Efforts to implement new active interventions that will increase public awareness of melanoma and the risks of tanning bed use are crucial; regulations on tanning bed use especially among those underage should be implemented.

The move away from animal models for skin safety testing is inevitable. It is a question of when, not if. As skin safety studies move away from traditional animal-based approaches, a number of replacement technologies are becoming available. Human skin in organ culture is one such technology. Organ-cultured skin has several features that distinguish it from other technologies. First and foremost, organ-cultured skin is real skin. Almost by definition, therefore, it approximates the intact skin better than other alternative models. Organ culture is an easy-to-use and relatively inexpensive approach to preclinical safety assessment. Although organ culture is not likely to replace high-throughput enzyme assays or monolayer culture/skin equivalent cultures for initial compound assessment, organ culture should find use when the list of compounds to be evaluated is small and when simpler models have narrowed the dose range. Organ-cultured skin also provides a platform for mechanistic studies.

Merkel cell carcinoma (MCC) is a rare cutaneous neuroendocrine neoplasm with a propensity for metastatic spread. When managing MCC, surgical excision is often the initial treatment. As MCC is generally radiosensitive, many institutions include adjuvant radiation therapy (RT) in their standard treatment protocols. In the absence of prospective randomized clinical trials, a number of retrospective reports suggest that adjuvant RT can improve local and regional recurrence rates. Here, we provide an overview of recent studies on the use of RT in MCC treatment and explore the limits of the current knowledge. Ultimately, the benefits and risks associated with using RT in the treatment of MCC remain poorly described and merit more rigorous investigation.

Melanogenesis is the unique process of producing pigmented biopolymers that are sequestered within melanosomes, which provides color to the skin, hair and eyes of animals and, in the case of human skin, also protects the underlying tissues from UV damage. We review the current understanding of melanogenesis, focusing on factors important to the biochemistry of pigment synthesis, the biogenesis of melanosomes, signaling pathways and factors that regulate melanogenesis, intramelanosomal pH, transport and transfer of melanosomes, and pigmentary disorders related to the dysfunction of melanosome-related proteins. Although it has been known for some time that many of the factors that affect melanogenesis are derived from keratinocytes, fibroblasts, endothelial cells, hormones, inflammatory cells and nerves, a number of new factors that are involved in that regulation have recently been reported, such as factors that regulate melanosome pH and ion transport.

Staphylococci are the most abundant skin-colonizing bacteria and the most important causes of nosocomial infections and community-associated skin infections. Molecular determinants of staphylococcal skin colonization include surface polymers and proteins that promote adhesion and aggregation, and a wide variety of mechanisms to evade acquired and innate host defenses. Antimicrobial peptides (AMPs) likely play a central role in providing immunity to bacterial colonization on human epithelia. Recent research has shown that staphylococci have a broad arsenal to combat AMP activity, and can regulate expression of AMP-resistance mechanisms depending on the presence of AMPs. While direct in vivo evidence is still lacking, this suggests that the interplay between AMPs and AMP resistance mechanisms during evolution had a crucial role in rendering staphylococci efficient colonizers of human skin.

The rapidly increasing incidence of melanoma, coupled with its highly aggressive metastatic nature, is of urgent concern. In order to design rational therapies, it is of critical importance to identify the genetic determinants that drive melanoma formation and progression. To date, signaling cascades emanating from the EGF receptor, c-MET and other receptors are known to be altered in melanoma. Important mutations in signaling molecules, such as BRAF and N-RAS, have been identified. In this review, some of the major genetic alterations and signaling pathways involved in melanoma will be discussed. Given the great deal of genetic heterogeneity observed in melanoma, it is likely that many more genetic determinants exist. Through the use of powerful genomic technologies, it is now possible to identify these additional genetic alterations in melanoma. A critical step in this analysis will be culling bystanders from functionally important drivers, as this will highlight genetic elements that will be promising therapeutic targets. Such technologies and the important points to consider in understanding the genetics of melanoma will be reviewed.

Nodal, an embryonic morphogen belonging to the TGF-β superfamily, is an important regulator of embryonic stem cell fate. We have recently demonstrated that Nodal is expressed significantly in aggressive melanoma. Surprisingly, expression of the Nodal coreceptor, Cripto-1, was detected in only a small fraction of the melanoma tumor cell population, indicating a primary role for Cripto-1-independent signaling of Nodal in melanoma. In this review, we discuss how regulatory factors present in an embryonic environment, such as Lefty, can downregulate Nodal expression and inhibit tumorigenicity and plasticity of melanoma cells. Our translational studies show that antibodies against Nodal are capable of repressing melanoma vasculogenic mimicry and of inducing apoptosis in melanoma tumors in an in vivo lung-colonization assay. Our previous work and ongoing studies suggest that Nodal may represent a novel diagnostic marker and therapeutic target in melanoma.

The main cause of death in melanoma patients is widespread metastases. Staging of melanoma is based on the primary tumor thickness, ulceration, lymph node and distant metastases. Metastases develop in regional lymph nodes, as satellite or in-transit lesions, or in distant organs. Lymph flow and chemotaxis is responsible for the homing of melanoma cells to different sites. Standard pathologic evaluation of sentinel lymph nodes fails to find occult melanoma in a significant proportion of cases. Detection of small numbers of malignant melanoma cells in these and other sites, such as adjacent to the primary site, bone marrow or the systemic circulation, may be enhanced by immunohistochemistry, reverse transcription PCR, evaluation of lymphatic vessel invasion and proteomics. In the organs to which melanoma cells metastasize, extravasation of melanoma cells is regulated by adhesion molecules, matrix metalloproteases, chemokines and growth factors. Melanoma cells may travel along external vessel lattices. After settling in the metastatic sites, melanoma cells develop mechanisms that protect them against the attack of the immune system. It is thought that one of the reasons why melanoma cells are especially resistant to killing is the fact that melanocytes (cells from which melanoma cells derive) are resistant to such noxious factors as ultraviolet light and reactive oxygen species. Targeted melanoma therapies are, so far, largely unsuccessful, and new ones, such as adjuvant inhibition of melanogenesis, are under development.

Melanocytes (MC) sit along the epidermal basal layer, largely quiescent except for constitutive melanin production. They are usually only activated after sun exposure. The recent paper by McGowan et al. (1) describes a novel mechanism by which melanocytes are induced to proliferate upon p53 activation in adjacent keratinocytes (KC). In this study, small subunit ribosomal protein mutations cause a dramatic activation of p53 that we propose mimics important aspects of the skin sunburn response after ultraviolet radiation (UVR) exposure. McGowan et al. show that the phenotype of their hyperpigmented mouse mutants results from p53-dependent upregulation of KITLG, a cytokine that binds to the KIT receptor on melanocytes and influences melanin synthesis, melanocyte proliferation, and dictates MC localization at the dermo-epidermal junction. These findings extend our knowledge about skin stress responses, in particular, how p53 activity in keratinocytes is central to the regulation of melanocyte behaviour.

Melanoma consists 4-5 % of all skin cancers, but it contributes to 71-80 % of skin cancers deaths. UV light affects cell and tissue homeostasis due to its damaging effects on DNA integrity and modification of expression of a plethora of genes. DNA repair systems protect cells from UV-induced lesions. Several animal models of melanoma have been developed (Xiphophorus, Opossum Monodelphis domestica, mouse models and human skin engrafts into other animals). This review discusses possible links between UV and genes significantly related to melanoma but does not discuss melanoma genetics. These include oncogenes, tumor suppressor genes, genes related to melanocyte-keratinocyte and melanocyte-matrix interaction, growth factors and their receptors, CRH, ACTH, α-MSH, glucocorticoids, ID1, NF-kappaB and vitamin D3.