Stephanie Wang

Destabilization of MYC/MYCN by the mitochondrial inhibitors, metaiodobenzylguanidine, metformin and phenformin

In the present study, we investigated the anticancer effects of the mitochondrial inhibitors, metaiodobenzylguanidine (MIBG), metformin and phenformin. 131I-MIBG has been used for scintigraphic detection and the targeted radiotherapy of neuroblastoma (NB), a pediatric malignancy. Non-radiolabeled MIBG has been reported to be cytotoxic to NB cells in vitro and in vivo. However, the mechanisms behind its growth suppressive effects have not yet been fully elucidated. Metformin and phenformin are diabetes medications that are being considered in anticancer therapeutics. We investigated the anticancer mechanisms of action of MIBG and metformin in NB. Our data revealed that both drugs suppressed NB cell growth and that the combination drug treatment was more potent. MIBG reduced MYCN and MYC expression in MYCN-amplified and non-MYCN-amplified NB cells in a dose- and time-dependent manner. Metformin was less effective than MIBG in destabilizing MYC/MYCN. The treatment of NB cells with metformin or MIBG resulted in an increased expression of genes encoding biomarkers for favorable outcome in NB [(ephrin (EFN)B2, EFNB3, EPH receptor B6 (EPHB6), neurotrophic tyrosine kinase, receptor, type 1 (NTRK1), CD44 and Myc-interacting zinc finger protein (MIZ-1)] and tumor suppressor genes [(early growth response 1 (EGR1), EPH receptor A2 (EPHA2), growth arrest and DNA-damage-inducible, beta (GADD45B), neuregulin 1 (NRG1), TP53 apoptosis effector (PERP) and sel-1 suppressor of lin-12-like (C. elegans) (SEL1L)]. Accordingly, metformin and MIBG augmented histone H3 acetylation in these cells. Phenformin also exhibited histone modification and was more effective than metformin in destabilizing MYC/MYCN in NB cells. Our data suggest that the destabilization of MYC/MYCN by MIBG, metformin and phenformin and their effects on histone modification are important mechanisms underlying their anticancer effects.

Compliance and phototherapy

When beginning a phototherapy regimen for a patient, consideration of compliance rates is important. Compliance to phototherapy can be affected by several factors, including the grade of discomfort and side effects from therapy, failure of previous therapies, accessibility and convenience to reach the phototherapy center, grade of improvement during phototherapy, patient relief due to light therapy, and rapport with staff. Understanding how these factors can affect patient adherence can allow for phototherapy regimens to be tailored in a manner that optimizes health outcomes and allows for proper patient selection.

Acquired microcystic lymphatic malformation of the distal upper extremity mimicking verrucae vulgaris.

An 18‐year‐old African American male with a history of congenital lymphedema of the right upper extremity presented for evaluation of multiple verrucous lesions on his right hand. Clusters of 2 to 4‐mm dome‐shaped vesicles were intermixed with scattered verrucous papules on the right forearm and the dorsal and palmar aspects of the hand. Histopathology of one the verrucous lesions showed well‐circumscribed areas of dilated lymphatic vascular channels with lymph in the lumen. The patient was diagnosed with microcystic lymphatic malformation, verrucous type. This article reviews the literature regarding reports of this variant of microcystic lymphatic malformation in the pediatric population.

Field Cancerization Therapies for Management of Actinic Keratosis: A Narrative Review

Actinic keratoses (AKs) are atypical, precancerous proliferations of keratinocytes that develop because of chronic exposure to ultraviolet (UV) radiation. Treatment of AK can be lesion-directed or field-directed. Field cancerization theory postulates that the skin surrounding AK is also at increased risk for possible malignant transformation since it has been exposed to the same chronic UV light. Field-directed therapies thus have the potential to address subclinical damage, reduce AK recurrence rates, and potentially reduce the risk of squamous cell carcinoma (SCC) development. Published clinical studies have found lesion clearance rates ranging from 81 to 91% for photodynamic therapy (PDT) with either aminolevulinic acid (ALA) or methylaminolevulinate (MAL). Clinical studies have also been published on various topical treatments. Complete clinical clearance (CCC) was significantly higher in patients treated with a combination of 5-fluorouracil and salicylic acid (5-FU–SA) than in the vehicle group across multiple studies, and CCC ranged between 46 and 48% following treatment with imiquimod. Additionally, treatment with diclofenac sodium (DFS) found reduction in lesion sizes to range from 67 to 75%. Reported results have been similar for another non-steroidal anti-inflammatory drug (NSAID), piroxicam, which has more cyclooxygenase (COX)-1 activity than DFS. Active treatments with ingenol mebutate were also significantly more effective than vehicle at clearing AK lesions. All treatments resulted in mild, localized skin reactions. PDT using conventional light sources was associated with increased severity of pain and/or discomfort, while PDT using daylight as the light source was associated with less pain and occasionally no pain at all. Though no widely accepted algorithm for the treatment of AKs exists, field-directed therapy can be particularly useful for treating photo-exposed areas containing multiple AKs. Additional research with more direct comparisons between these field-directed therapies will help clinicians determine the best therapeutic approach. Here, we provide a balanced and comprehensive narrative review of the literature, considering both light-based and topical therapies with a focus on their field-therapy aspects, and propose a therapeutic algorithm for selecting an appropriate treatment in the clinical setting.

Phototherapy in cosmetic dermatology.

Light therapy has been incorporated into the art of healing and cosmesis for thousands of years and currently has found utility in many areas of medicine. Various modalities of cosmetic phototherapy are detailed, as well as the indications and mechanism of action for each modality. These modalities can be used to treat many common cosmetic conditions, including acne vulgaris, solar lentigo, and melasma. Phototherapy is considered a safe and effective option in the treatment of many of these disorders.

Use of a melanoma simulation model in a dermatology Objective Structured Clinical Examination station

certainly been revolutionized. From a personal perspective, I look forward to reading formal research around the topic – the open book statistical assessment was certainly not a walk in the park. The format of the assessment required significant theoretical application. The book simply allowed for refreshment of factual knowledge. The assessment relied on candidates being able to interpret data provided and comment accordingly. For example, research data with confidence intervals, p values, odds ratios, Wald and degrees of freedom values featured heavily. In addition, candidates were asked to comment on assumptions made, potential confounding variables and additional univariate and multivariate tests of choice, as well as construct potential tables for data we would like to collect for specific research questions. In medical practice, postgraduate training often relies on referring to current literature when managing a patient appropriately, particularly evidence-based specialty guidelines. Of course, it is important for candidates to learn the theory; but I wonder whether the use of open book assessments could potentially be a good thing. If constructed properly, they could provide a more suitable platform of theory application as opposed to simple recall.

Generalized, pruritic skin eruption in an immunocompromised patient

A 50-year-old African-American female with a past medical history significant for human immunodeficiency virus (HIV) and non-adherence to HAART therapy, was admitted for failure to thrive and a generalized, pruritic skin eruption. The patient first noticed the eruption on her feet a few months prior to admission. Within days, it had spread to her torso, upper extremities, and scalp. On physical examination, she had well-demarcated, erythematous and scaly, confluent plaques involving the torso, upper and lower extremities (Figure 1). In addition, she had thick, hyperkeratotic plaques on the palms and soles as well as dystrophic fingernails (Figure 2). Skin scrapings were performed and histopathology evaluation was obtained (Figure 3). What is your diagnosis? Generalized, pruritic skin eruption in an immunocompromised patient