Melanoma
Automated Dermatological Diagnosis: Hype or Reality?
In this issue of the Journal of Investigative Dermatology, Han et al. (2018) have made a landmark contribution to the application of artificial intelligence (AI) in dermatologic diagnosis. Although previous studies have reported that computer algorithms can successfully diagnose skin cancer from medical images with human equivalency (Esteva et al., 2017; Ferris et al., 2015; Marchetti et al., 2018; Menzies et al., 2005), Han et al. have made their computer algorithm publicly available for external testing.Association between Body Mass Index, C-Reactive Protein Levels, and Melanoma Patient Outcomes
Obesity is a known risk factor for cancer development (Arnold et al., 2016; Basen-Engquist and Chang, 2011; Renehan et al., 2015) and death (Calle et al., 2003). Obesity has been associated with an increased risk of developing melanoma in men (Sergentanis et al., 2013) and with thicker primary melanomas (Skowron et al., 2015). The inflammatory adipokine leptin promotes melanoma progression in mice (Amjadi et al., 2011; Brandon et al., 2009; Gogas et al., 2008); elevated leptin levels may predict melanoma sentinel node metastasis (Oba et al., 2016).Noninvasive Determination of Melanoma Depth using a Handheld Photoacoustic Probe
When a clinically suspicious pigmented lesion is biopsied and histologic examination shows melanoma, tumor depth, or Breslow’s depth (BD), is the key parameter that both determines surgical margins for definitive excision and serves as an indication to perform sentinel lymph node biopsy (Smith and MacNeil, 2011). Optimally, BD is measured during an initial excisional biopsy that includes the entire lesion. However, in many cases an incisional biopsy is performed that takes a sample of only a portion of the tumor, possibly resulting in an inaccurate measurement (Guitera and Menzies, 2011; Sellheyer et al., 2010).CXCR3 Depleting Antibodies Prevent and Reverse Vitiligo in Mice
Vitiligo is a disfiguring skin disease in which melanocytes with intrinsic abnormalities are targeted and destroyed by autoreactive CD8+ T cells in the epidermis, resulting in patchy depigmentation (Palermo et al., 2001; van den Boorn et al., 2009, and reviewed in Richmond et al., 2013). Although it is one of the most common autoimmune diseases, affecting 1% of the population worldwide, there are no Food and Drug Administration-approved treatments. Previous work from our lab has shown that CD8+ T-cell recruitment to the skin in a mouse model of vitiligo is dependent on IFNγ (Harris et al., 2012) and the downstream CXCR3 chemokine system (Rashighi et al., 2014).Consensus of Melanoma Gene Expression Subtypes Converges on Biological Entities
Identification of recurrent mutation in the BRAF oncogene in melanoma has led to the development of highly selective kinase inhibitors (Larkin et al., 2014). Although dramatic treatment responses are initially observed, responses are rarely durable. The mutational classification based on BRAF, NRAS, and NF1 mutations that has been established, however, is nonoverlapping with classification derived from gene expression profiling (The Cancer Genome Atlas Network [TCGA], 2015; Jönsson et al., 2010).Telomerase Expression by Aberrant Methylation of the TERT Promoter in Melanoma Arising in Giant Congenital Nevi
Telomeres are tandem repeats of the noncoding DNA structures at the end of human chromosomes that protect the coding DNA and the integrity of the genome (Blackburn, 1991). The ability to sustain telomere length confers unlimited proliferative capacity to cancer cells. In most cancers telomere length is maintained by the activity of the enzyme telomerase (Kim et al., 1994), whose catalytic subunit is encoded by the telomerase reverse transcriptase (TERT) gene. However, until recently, the underlying mechanisms for telomerase activation in cancer cells were largely unknown.Validity of Self-Reported Psoriasis in a General Population: The HUNT Study, Norway
A high prevalence of psoriasis has been reported in Norway, ranging from 4.8% to 11.8% (Bo et al., 2008; Danielsen et al., 2013; Kavli et al., 1985; Parisi et al., 2013). Prevalence estimates depend crucially on the validity of questionnaires (Jagou et al., 2006; Kurd and Gelfand, 2009; Lima et al., 2013; Plunkett et al., 1999; Rea et al., 1976; Wolkenstein et al., 2009). We aimed to validate self-reported psoriasis in a large population-based study in Norway using clinical skin examination performed by dermatologists as the gold standard and also to estimate the validation-based prevalence of psoriasis in a general Norwegian population.Melanoma-Directed Activation of Apoptosis Using a Bispecific Antibody Directed at MCSP and TRAIL Receptor-2/Death Receptor-5
Tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) is an immune effector protein that induces apoptosis in virus-infected and cancer cells by activating death receptor-4 (DR4) and/or death receptor-5 (DR5) without deleterious activity toward DR4/DR5-expressing normal cells (Ashkenazi et al., 2008). Consequently, DR4/DR5 agonists are promising anticancer agents. Treatment with “first-generation” DR4/DR5-targeted therapeutics, such as recombinant human soluble tumor necrosis factor-related apoptosis-inducing ligand (rhTRAIL) and agonistic DR4/DR5 antibodies, was well tolerated but had disappointing clinical activity (Ashkenazi, 2015).
