Targeting Dysregulated Ion Channels in Liver Tumors with Venom Peptides.

The regulation of cellular processes by ion channels has become central to the study of cancer mechanisms. Designing molecules that can modify ion channels specific to tumor cells is a promising area of targeted drug delivery and therapy. Despite their potential in drug discovery, venom peptides-a group of natural products-have largely remained understudied and under-characterized. In general, venom peptides display high specificity and selectivity for their target ion channels. Therefore, they may represent an effective strategy for selectively targeting the dysregulation of ion channels in tumor cells. This review examines existing venom peptide therapies for different cancer types and focuses on the application of snail venom peptides in hepatocellular carcinoma (HCC), the most common form of primary liver cancer worldwide. We provide insights into the mode of action of venom peptides that have been shown to target tumors. We also explore the benefit of using new computational methods like de novo protein structure prediction to screen venom peptides and identify potential druggable candidates. Finally, we summarize the role of cell culture, animal, and organoid models in developing effective therapies against HCC and highlight the need for creating models that represent the most disproportionately affected ethnicities in HCC.

Primary Cutaneous Epithelioid Mesenchymal Tumor With a Novel ATP2B4::GLI1 Gene Fusion.

ABSTRACT: GLI1 gene alterations (rearrangement or amplification) have been found in several bone and soft tissue tumors including pericytic tumors, gastric plexiform fibromyxoma, gastroblastoma, and a various group of epithelioid tumors with regional recurrence or distant metastasis. In this article, we describe a case of primary cutaneous epithelioid mesenchymal tumor harboring hitherto not reported ATP2B4::GLI1 gene fusion. A 42-year-old man presented with a growing firm lesion on the left postauricular scalp. Microscopically, the shave biopsy specimen revealed a dermal-based nodular proliferation of relatively monotonous epithelioid cells with round to ovoid nuclei and pale eosinophilic cytoplasm, accompanied by prominent stromal vasculature. Significant cytologic atypia, necrosis, and mitotic activity were absent. The tumor cells were partially positive for CD34 and S-100 protein, but were negative for other markers, including SOX-10, keratins, and myogenic markers. An ATP2B4::GLI1 gene fusion was identified by next-generation sequencing. Array CGH was also performed, but it did not show relevant chromosomal copy number changes. Awareness of this rare cutaneous tumor, and thus, reporting of additional cases is necessary for further delineating its full clinicopathologic spectrum.

Chrysiasis: Gold Aggregates Around a Nevus and Osteoma Cutis.

ABSTRACT: Parenteral gold has historically been used to treat several conditions, including rheumatoid arthritis. Gold administration leads to a variety of cutaneous reactions, including chrysiasis, which is a permanent blue-grey hyperpigmentation of the skin due to dermal gold deposition. In this report, we describe the case of a patient who received parenteral gold injections 22 years before the onset of her chrysiasis for the treatment of rheumatoid arthritis. Biopsy of the macules showed dermal gold deposits aggregating around a melanocytic nevus, as well as around preexisting osteoma cutis. To the authors' knowledge, this is the first report in the literature describing a case of chrysiasis with gold deposits concentrated around a melanocytic nevus and an area of osteoma cutis.

Vitiligo and Melanoma-Associated Vitiligo: Understanding Their Similarities and Differences.

BACKGROUND: There has been a significant increase in the number and efficacy of therapies for advanced melanoma. Immunotherapies, such as anti-cytotoxic T-lymphocyte antigen-4 and programmed cell death-1 inhibitors, have improved the prognosis for patients with advanced melanoma. While spontaneous melanoma-associated vitiligo is a known phenomenon, the occurrence of melanoma-associated vitiligo following melanoma therapy is now recognized to associate with favorable outcomes. OBJECTIVE: The objective of this article is to provide a comprehensive literature review of melanoma-associated vitiligo and explore the insights these findings provide about the pathobiology of vitiligo and mechanisms underlying melanoma therapies. METHODS: PubMed and Science Direct databases were searched for studies pertaining to melanoma-associated vitiligo. The 36 studies reviewed included meta-analyses (n = 2), prospective cohort studies (n = 4), prospective observational studies (n = 3), retrospective studies (n = 12), case series (n = 2), and case reports (n = 13). RESULTS: The basic mechanisms underlying melanoma-associated vitiligo and vitiligo may be shared. Characterization of these mechanisms will identify new biomarkers and therapeutic targets for both melanoma and vitiligo. CONCLUSIONS: Co-opting the immune system to target tumor antigens highlights the potential overlap between anti-tumor immunity and autoimmunity. The development of vitiligo-like depigmentation in association with immunotherapy for melanoma may provide insights into both the immune response against melanoma as well as the pathogenesis of vitiligo.

Comparison of Skin Cancer Incidence in Caucasian and Non-Caucasian Liver Vs. Lung Transplant Recipients: A Tale of Two Regimens.

BACKGROUND: Organ transplantation is a significant risk factor for the development of skin cancer. The impact of skin type, immunosuppressive regimens, and photosensitizing agents requires further study. OBJECTIVE: The objective of this study was to compare skin cancer development between Caucasian and non-Caucasian transplant recipients at the University of Southern California. METHODS: We performed a retrospective chart review of lung and liver transplantations to determine the incidence of post-transplant skin cancer. Participants included patients who underwent lung or liver transplantation between 2005 and 2013 at our institution. Patients included in the study were limited to those who survived through the study observation period. RESULTS: We analyzed 475 patients who underwent transplantation, including 370 liver transplant recipients and 105 lung transplant recipients. Among these, 46.3% identified as Caucasian, while 53.7% were non-Caucasian. Over a mean follow-up of 7.9 years, 11.8% of Caucasian patients developed at least one skin cancer, compared with 2.7% of non-Caucasians (p < 0.001). However, irrespective of race, skin cancer development was significantly greater in lung compared with liver transplant recipients (20.0% vs. 3.2%, p < 0.001). The standard immunosuppressive and prophylactic regimens were mycophenolate mofetil and tacrolimus based for both transplants. Mycophenolate mofetil was maintained throughout the course in lung transplant patients, whereas this agent was reduced and terminated when possible in liver transplant recipients. In addition, during the years examined, voriconazole, a known photosensitizing agent, was used in lung transplant recipients to prevent aspergillosis. CONCLUSIONS: Fair skin type increases post-transplant skin cancer development, irrespective of the immunosuppressive regimen. A higher risk of skin cancer is associated with different regimens; in particular photosensitizing agents may increase risk in transplant recipients.

The Role of Elastic Fibers in Scar Formation and Treatment.

BACKGROUND: Laser therapy is a continuously evolving treatment option for scars, and the underlying therapeutic mechanisms continue to be elucidated. OBJECTIVE: To comprehensively review the literature to summarize the role of elastin in the formation scars, as well as treatment via therapeutic lasers. METHODS: Review of the PubMED/MEDLINE database for available studies pertaining to the role of elastic fibers in scar formation and after laser-based therapy. RESULTS: The loss and disorganization of elastic fiber components plays a role in the development of atrophic, hypertrophic, and keloid scars. While the majority of histologic studies focus on the underlying changes in collagen, neoelastogenesis and reorganization of elastic fibers have also been demonstrated in studies using ablative, nonablative, and fractional laser devices for the treatment of scars. CONCLUSION: Production of novel elastin and normalization of elastic fiber organization occur after a variety of resurfacing procedures to treat scarring. As the treatment modalities to manage scars continue to evolve, further characterization of the role of elastin in the skin and in scar formation is merited.

Literature Review of Cosmetic Procedures in Men: Approaches and Techniques are Gender Specific.

The proportion of men receiving non-surgical cosmetic procedures has risen substantially in recent years. Various physiologic, anatomic, and motivational considerations differentiate the treatments for male and female patients. Nevertheless, research regarding approaches to the male cosmetic patient is scarce. We sought to provide an overview and sex-specific discussion of the most popular cosmetic dermatologic procedures pursued by men by conducting a comprehensive literature review pertaining to non-surgical cosmetic procedures in male patients. The most common and rapidly expanding non-surgical interventions in men include botulinum toxin, filler injection, chemical peels, microdermabrasion, laser resurfacing, laser hair removal, hair transplantation, and minimally invasive techniques for adipose tissue reduction. Important sex-specific factors associated with each of these procedures should be considered to best serve the male cosmetic patient.

Microneedling: A Comprehensive Review.

BACKGROUND: Microneedling is a minimally invasive procedure that uses fine needles to puncture the epidermis. The microwounds created stimulate the release of growth factors and induce collagen production. The epidermis remains relatively intact, therefore helping to limit adverse events. The indications for microneedling therapy have grown significantly, and it is becoming a more widely used treatment in dermatology. OBJECTIVE: A comprehensive review of microneedling in human subjects and its applications in dermatology. METHODS AND MATERIALS: A search was performed using PubMed/MEDLINE and Science Direct databases. Search terms included "microneedling," "needling," and "percutaneous collagen induction." All available studies involving human subjects were included in the discussion, with priority given to prospective, randomized trials. RESULTS: Studies demonstrate microneedling efficacy and safety for the treatment of scars, acne, melasma, photodamage, skin rejuvenation, hyperhidrosis and alopecia and for facilitation of transdermal drug delivery. While permanent adverse events are uncommon, transient erythema and postinflammatory hyperpigmentation are more commonly reported. CONCLUSION: Microneedling appears to be an overall effective and safe therapeutic option for numerous dermatologic conditions. Larger and more randomized controlled trials are needed to provide greater data on the use of microneedling for different dermatologic conditions in different skin types.

Dermal Titanium Dioxide Deposition Associated With Intralesional Triamcinolone Injection.

Cutaneous discoloration secondary to dermal deposition of titanium dioxide (TiO2) particles is recognized but seldom reported in the literature. In this report, the authors describe the case of a 61-year-old gentleman, with a long history of alopecia areata, who presented with numerous, discrete dark blue macules on the scalp. Scanning electron microscopy with energy dispersive x-ray spectroscopy analysis ultimately identified the macules as deposits of TiO2. The patient had a history of intralesional triamcinolone injections for management of alopecia areata. A sample of generic 0.1% triamcinolone acetonide paste was analyzed and found to contain many TiO2 particles analogous to those seen in the patient's biopsy sample. To the authors' knowledge, this is the first reported case of TiO2 deposition in the dermis likely resulting from topical combined with intralesional triamcinolone injection.

CD30+ lymphoproliferative disorder with spindle-cell morphology.

Lymphomatoid papulosis (LyP) is classified as a CD30+ primary cutaneous lymphoproliferative disease. The phenotypic variability along the spectrum of CD30+ lymphoproliferative diseases is highlighted by the distinct histologic subtypes of LyP types A, B, C, and the more recently described types D, E, and F. We report the case of an elderly woman with a clinical presentation and histopathologic findings consistent with LyP, whose atypical CD30+ infiltrate uniquely demonstrated a spindle-cell morphology. To our knowledge, this is the first reported case of LyP characterized by CD30+ spindle-shaped cells, and may represent a new and distinct histologic variant of LyP.

Comparison of Childhood Vitiligo Presenting with or without Associated Halo Nevi.

BACKGROUND: Previous studies have characterized differences in vitiligo associated with halo nevi, but the features of vitiligo presenting with halo nevus in children have yet to be fully described. AIMS: We sought to provide an epidemiologic and clinical comparison of cases of childhood vitiligo presenting with or without associated halo nevi. MATERIALS AND METHODS: This was a retrospective chart review of children diagnosed with vitiligo in an academic pediatric dermatology practice from January 1990 to November 2014. The characteristics of children with vitiligo with or without associated halo nevi were compared. RESULTS: Halo nevi were identified in 55 (26%) of 208 children with vitiligo. Patients with halo nevi were significantly more likely to be male and develop vitiligo at a later age. Children with vitiligo associated with halo nevi were more likely to present with generalized vitiligo, defined according to the presence of bilateral macules. DISCUSSION: There was no significant association between groups in the percentage of body surface area with vitiligo or family history of vitiligo or autoimmune diseases. Patients with halo nevi were no more likely to develop new areas of vitiligo during the follow-up period, but there was a nonsignificant trend toward a higher rate of repigmentation in vitiligo associated with halo nevus. CONCLUSION: Halo nevi are a common finding in children with vitiligo. The presence of a halo nevus in a child with vitiligo is associated with generalized vitiligo. The presence of a halo nevus does not significantly alter the risk of disease progression and rate of treatment.

Acne scarring: A review of available therapeutic lasers.

BACKGROUND AND OBJECTIVE: The utilization of lasers in dermatology has greatly expanded in recent decades. Acne scarring is a common indication in which lasers play an important therapeutic role. STUDY DESIGN/MATERIALS AND METHODS: Available lasers include traditional ablative lasers, such as carbon dioxide and erbium lasers, traditional non-ablative lasers, such as neodymium, diode, alexandrite, pulsed dye lasers and intense pulse light, as well as both ablative, and non-ablative fractional laser systems. CONCLUSION: We sought to provide a framework for understanding the various types of lasers available to treat acne scars and review the primary literature pertaining to the efficacy, safety, and advantages of each laser discussed.

Psoriasis and the Risk of Depression in the US Population: National Health and Nutrition Examination Survey 2009-2012.

IMPORTANCE: Psoriasis is a risk factor for depression. Depression may also trigger or exacerbate psoriasis. The relationship between psoriasis and depression, however, remains to be fully explored. OBJECTIVE: To investigate the association between psoriasis and major depression in the US population. DESIGN, SETTING, AND PARTICIPANTS: Population-based study using participants in the National Health and Nutrition Examination Survey from 2009 through 2012. MAIN OUTCOMES AND MEASURES: Diagnosis of major depression based on the Patient Health Questionnaire-9. RESULTS: We identified 351 (2.8%) cases of psoriasis and 968 (7.8%) cases of major depression among 12,382 US citizens included in our study. Fifty-eight (16.5%) patients with psoriasis met criteria for a diagnosis of major depression. The mean (SD) Patient Health Questionnaire-9 score was significantly higher among patients with a history of psoriasis than those without psoriasis (4.54 [5.7] vs 3.22 [4.3], P < .001). Psoriasis was significantly associated with major depression, even after adjustment for sex, age, race, body mass index, physical activity, smoking history, alcohol use, history of myocardial infarction (MI), history of stroke, and history of diabetes mellitus (OR, 2.09 [95% CI, 1.41-3.11], P < .001). Interaction term analyses involving patients with a history of both psoriasis and a cardiovascular event, specifically MI or stroke, did not reveal a synergistically increased risk of major depression (psoriasis and MI: OR, 1.09 [95% CI, 0.28-3.60], P = .91; psoriasis and stroke: OR, 0.67 [95% CI, 0.12-3.66], P = .63). In adjusted multivariable models, the risk of major depression was not significantly different between patients with limited vs extensive psoriasis (OR, 0.66 [95% CI, 0.18-2.44], P = .53). CONCLUSIONS AND RELEVANCE: Self-reported history of psoriasis was independently associated with major depression as assessed by a validated screening tool, even when controlling for comorbidities. History of cardiovascular event did not modify the risk of major depression for patients with psoriasis. The severity of psoriasis was unrelated to the risk of major depression. Therefore, all patients with psoriasis, regardless of severity, may be at risk for major depression.

Alternative Systemic Treatments for Vitiligo: A Review.

Vitiligo is a common, acquired disorder of skin pigmentation that can significantly impact quality of life. It often represents a therapeutic challenge, which has resulted in interest in alternative treatments such as herbal and vitamin supplements. In this review, we provide an overview of the most commonly studied complementary agents, describe proposed mechanisms of action, identify potential adverse effects, and discuss the primary evidence supporting their use. Our discussion focuses on L-phenylalanine, Polypodium leucotomos, khellin, Ginkgo biloba, and vitamins and minerals, including vitamins B12, C, and E, folic acid, and zinc used as monotherapy or in combination with other treatments for the management of vitiligo.

Early-onset childhood vitiligo is associated with a more extensive and progressive course.

OBJECTIVES: Vitiligo commonly presents in children, with half of all cases developing before 20 years of age. Although studies have characterized differences between pediatric and adult vitiligo, little is known about vitiligo presenting in early childhood. The purpose of this study was to compare clinical features of early-onset (<3 years old) and later-onset (3-18 years old) childhood vitiligo. METHODS: This retrospective case series examined patients given a diagnosis of vitiligo in a pediatric dermatology practice at an academic medical center from 1990 to 2014. Characteristics of the early- and later-onset groups were compared by χ(2) and t test for categorical and continuous variables, respectively. RESULTS: Of the 208 children in the study, 31 had early-onset and 177 had later-onset disease. Early-onset vitiligo was associated with higher percentages of body surface area involvement and increased rates of disease progression during an average 1.9 years of follow-up. There were no significant differences between the 2 groups in repigmentation, vitiligo type, halo nevi, gender ratio, or personal and family history of autoimmune diseases. LIMITATIONS: This was a retrospective, single-institution study. CONCLUSION: Patients given a diagnosis of vitiligo at younger ages tend to have more extensive and progressive disease.