Melanoma is the deadliest form of skin cancer. In the early stages, melanoma can be treated successfully with surgery alone and survival rates are high, but after metastasis survival rates drop significantly. Therefore, early and correct diagnosis is key for ensuring patients have the best possible prognosis. Melanoma misdiagnosis accounts for more pathology and dermatology malpractice claims than any cancer other than breast cancer, as an early misdiagnosis can significantly reduce a patient’s chances of survival. As far as treatment for metastatic melanoma goes, there have been several new drugs developed over the last 10 years that have greatly improved the prognosis of patients with metastatic melanoma, however, a majority of patients do not show a lasting response to these treatments. Thus, new biomarkers and drug targets are needed to improve the accuracy of melanoma diagnosis and treatment. This article will discuss the major advancements of melanoma diagnosis and treatment from antiquity to the present day.

Over-expression of the translesion synthesis polymerase (TLS pol) hpol κ in glioblastomas has been linked to a poor patient prognosis; however, the mechanism promoting higher expression in these tumors remains unknown. We determined that activation of the aryl hydrocarbon receptor (AhR) pathway in glioblastoma cells leads to increased hpol κ mRNA and protein levels. We blocked nuclear translocation and DNA binding by the AhR in glioblastoma cells using a small-molecule and observed decreased hpol κ expression. Pharmacological inhibition of tryptophan-2,3-dioxygenase (TDO), the enzyme largely responsible for activating the AhR in glioblastomas, led to a decrease in the endogenous AhR agonist kynurenine (Kyn) and a corresponding decrease in hpol κ protein levels. Importantly, we discovered that inhibiting TDO activity, AhR signaling, or suppressing hpol κ expression with RNA interference led to decreased chromosomal damage in glioblastoma cells. Epistasis assays further supported the idea that TDO activity, activation of AhR signaling and the resulting over-expression of hpol κ function primarily in the same pathway to increase endogenous DNA damage. These findings indicate that up-regulation of hpol κ through glioblastoma-specific TDO activity and activation of AhR signaling likely contributes to the high levels of replication stress and genomic instability observed in these tumors.

Background Restriction of food intake is a central feature of anorexia nervosa (AN) and other eating disorders, yet also occurs in the absence of psychopathology. The neural mechanisms of restrictive eating in health and disease are unclear. Methods This study examined behavioral and neural mechanisms associated with restrictive eating among individuals with and without eating disorders. Dietary restriction was examined in four groups of women (n = 110): healthy controls, dieting healthy controls, patients with subthreshold (non-low weight) AN, and patients with AN. A Food Choice Task was administered during fMRI scanning to examine neural activation associated with food choices, and a laboratory meal was conducted. Results Behavioral findings distinguished between healthy and ill participants. Healthy individuals, both dieting and non-dieting, chose significantly more high-fat foods than patients with AN or subthreshold AN. Among healthy individuals, choice was primarily influenced by tastiness, whereas, among both patient groups, healthiness played a larger role. Dorsal striatal activation associated with choice was most pronounced among individuals with AN and was significantly associated with selecting fewer high-fat choices in the task and lower caloric intake in the meal the following day. Conclusions A continuous spectrum of behavior was suggested by the increasing amount of weight loss across groups. Yet, data from this Food Choice Task with fMRI suggest there is a behavioral distinction between illness and health, and that the neural mechanisms underlying food choice in AN are distinct. These behavioral and neural mechanisms of restrictive eating may be useful targets for treatment development.

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Objective: The aim of this study was to examine the relationship between habit strength and clinical features of anorexia nervosa (AN). Habit strength, separate from intention, relates to the persistence of behavior, and is measured by the Self-Report Habit Index (SRHI). We hypothesized that habit strength would be greater among individuals with AN than healthy controls (HC) and that habit strength would be associated with duration and severity of illness.Method: Participants were 116 women with AN (n = 69) and HC (n = 47) who completed the SRHI, the Eating Disorder Examination-Questionnaire (EDE-Q), and a multi-item laboratory meal. The SRHI assessed four domains and these subscales were averaged for the total score.Results: Individuals with AN demonstrated significantly greater habit strength than HC in the total score (t 114 = 7.00, p < .01), and within each domain (restrictive eating, compensatory behavior, delay of eating, and rituals). Total SRHI score was significantly associated with EDE-Q scores for both AN and HC groups (r AN = .59, p AN = <.001; r HC = .32, p HC = .030). Among patients, there was a significant association between SRHI and duration of illness (r = .38, p = .001). There was no significant association between SRHI and caloric intake (r AN = −.20, p AN = .10; r HC = −.25, p HC = .09).Discussion: Habit strength was related to chronicity and severity of AN, suggesting that habit formation may play an important role in illness. These data suggest avenues for mechanism research and treatment development. K E Y W O R D Sanorexia nervosa, duration of illness, eating disorders, habit, Self-Report Habit Index