p300 KAT regulates SOX10 stability and function in human melanoma.

SOX10 is a lineage-specific transcription factor critical for melanoma tumor growth, while SOX10 loss-of-function drives the emergence of therapy-resistant, invasive melanoma phenotypes. A major challenge has been developing therapeutic strategies targeting SOX10's role in melanoma proliferation, while preventing a concomitant increase in tumor cell invasion. Here, we report that the lysine acetyltransferase (KAT) EP300 and SOX10 gene loci on Chromosome 22 are frequently co-amplified in melanomas, including UV-associated and acral tumors. We further show that p300 KAT activity mediates SOX10 protein stability and that the p300 inhibitor, A-485, downregulates SOX10 protein levels in melanoma cells via proteasome-mediated degradation. Additionally, A-485 potently inhibits proliferation of SOX10+ melanoma cells while decreasing invasion in AXLhigh/MITFlow melanoma cells through downregulation of metastasis-related genes. We conclude that the SOX10/p300 axis is critical to melanoma growth and invasion, and that inhibition of p300 KAT activity through A-485 may be a worthwhile therapeutic approach for SOX10-reliant tumors.

Urticaria Pigmentosa Without Pruritus.

Mastocytosis is a group of disorders characterized by the pathologic accumulation of mast cells in various tissues. One example of mastocytosis is urticaria pigmentosa, which presents with mastocytomas that can cause hives and, when irritated, pruritus. To our knowledge, we are describing the first case of urticaria pigmentosa without pruritus. The patient had a positive Darier's sign, stated that they never felt itchy, and denied ever using a topical steroid or antihistamine. Although our patient declined additional testing, patients like this may benefit from a detailed evaluation of their sensory system through both quantitative sensory testing and genetic analysis. J Drugs Dermatol. 2024;23(3):     doi:10.36849/JDD.7558e.

Keratinocyte Carcinoma Chemoprevention With a Combination of Imiquimod, 5-Fluorouracil, and Tretinoin.

BACKGROUND: The incidence of keratinocyte carcinomas (KCs), comprising basal and squamous cell carcinomas, is rising in the United States. Chemoprevention is one modality by which patients can reduce the incidence of KCs. METHODS: We performed a retrospective review of 327 patients who employed a combination of imiquimod 5% cream, 5-fluorouracil 2% solution, and tretinoin 0.1% cream in a field therapy regimen over the face/ears or scalp for chemoprevention. RESULTS: Patients had dramatically lower odds of having KCs in the treatment location (face/ears or scalp) in the one-year period after field treatment than in the one-year period preceding field treatment (OR=0.06, 95% CI: [0.02, 0.15]). Patients were also at lower odds of having KCs in non-treated areas the year after field treatment than in the year preceding it (OR=0.25, 95% CI: [0.14, 0.42]). Additionally, fewer cryotherapy sessions were performed for actinic keratoses in the treatment areas in the year after treatment (mean=1.5, SD=1.21) than the year preceding treatment (mean=2.3, SD=0.99; t=11.68, P<0.001). CONCLUSIONS: A combination of imiquimod 5% cream, 5-fluorouracil 2% solution, and tretinoin 0.1% cream were effective at reducing the incidence of new KCs for at least one year. Individualized treatment application frequency allowed for increased patient adherence. Prospective studies evaluating combination topical treatments for chemoprevention of KCs are needed to further assess the treatment effects found in this study. J Drugs Dermatol. 2023;22(5): doi:10.36849/JDD.7334.

Epigenetics and cutaneous neoplasms: from mechanism to therapy.

Epigenetics encompasses heritable, reversible gene expression patterns that do not arise from mutations in genomic DNA but, rather, are regulated by DNA methylation, histone modifications, RNA modifications and ncRNAs; and epigenetic dysregulation is increasingly recognized as a mechanism of neoplastic disease progression as well as resistance to cancer therapy. This review article focuses on epigenetic modifications implicated in the progression and therapeutic resistance of common cutaneous malignancies, including basal cell carcinoma, squamous cell carcinoma, T-cell lymphoma and malignant melanoma, with an emphasis on therapeutic strategies that may be used to target such disease-associated alterations.

Epigenetics involves the study of how genes can be turned on or off by factors that affect how these genes are packaged and regulated. In cancer, there are often epigenetic changes that contribute to the formation of tumors. Many of these epigenetic changes, some of which can be passed down through generations, increase the risk of skin cancers such as basal cell carcinoma, squamous cell carcinoma, T-cell lymphoma and malignant melanoma. Emerging therapies designed to target these epigenetic changes may be effective treatments for these types of skin cancers. Researchers are currently investigating how to best use these therapies to help the ever-increasing number of people with skin cancer.

Sun exposure and protection practices among Florida college marching band members and alumni: a cross-sectional study.

In the USA, skin cancer is the most common cancer, more than all other cancers combined. Skin cancer may be prevented by using sun protection. This is particularly important in 18-29-year-olds who, compared to older individuals, experience sunburns more frequently. Moreover, in locations close to the equator, such as Florida, people are at an increased risk of developing melanoma. College marching band members spend a significant amount of time in the sun, as much as 25 h weekly practicing and performing at games, yet little is known about this population. We examined and compared sun exposure and protection practices among Florida college marching band members and alumni. In 2020, anonymous cross-sectional web-based surveys were distributed via email and private Facebook groups. A total of 859 members and alumni of five Florida university marching bands participated. Questionnaires assessed demographic characteristics, sun protection behaviors, as well as history of sunburn and skin cancer. Analyses of variance and multiple linear regression analyses were employed to compare sun protection practices between band members and alumni. During sunny day practices, only 16.1% (63/391) of alumni and 27.1% (127/468) of current band members always wore sunscreen. In the multiple linear regression, after adjusting for gender, race/ethnicity, and family history of skin cancer, alumni, who participated in marching band practices within the past 50 years, were significantly less likely to wear sunscreen or hats compared to current band members. Overall, men were less likely to wear sunscreen but were more likely to wear hats and shirts with sleeves that cover their shoulders compared to women. Compared to the general US population in 2017 (0.38%), alumni of Florida college marching bands in 2020 (2.04%) have a self-reported increase in melanoma prevalence of 1.66%. Of note, melanoma diagnoses were only reported by alumni who self-identified as non-Hispanic white; none of the non-Hispanic black, Hispanic, or other alumni reported a melanoma diagnosis. As skin cancer incidence continues to rise, it is critical that leaders in the marching band community continually address unprotected sun exposure, by promoting protective practices, as well as modifying attitudes and behaviors regarding sun exposure and protection.

Factors influencing postmortem disposition of cryopreserved sperm in men undergoing fertility preservation.

OBJECTIVE: To study the factors that influence men's disposition towards post-mortem disposition of their cryopreserved gametes. DESIGN: A retrospective chart review of sperm cryopreservations between June 2016 and January 2020 was performed. All patients ≥ 18 years of age were included. Samples intended for donation or records with an unspecified reason for preservation were excluded. SETTING: A large academic health center. PATIENTS: Participants' (n=217) mean age was 35.8 ± 10.8 years. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Patients' reason for undergoing sperm cryopreservation, method of retrieval, and whether they chose to have the sample preserved or discarded post-mortem. RESULTS: A total of 217 men were analyzed; mean age was 35.8 ± 10.8 years. Of those, 176 (81.1%) men decided to preserve their sperm for a spouse and 41 (18.9%) elected to have the sample discarded when choosing the fate of their cryopreserved sample should they die. There was no significant difference in disposition towards sample fate based on age or method of collection. However, there was a significant difference based on the "reason for cryopreservation" (p = 0.001). We found that compared to patients that underwent sperm cryopreservation due to cancer-related treatments, the patients that underwent sperm banking prior to vasectomy were more inclined to discard the sample (OR = 3.45, 95% CI: 1.16 - 10.27, p = 0.026). Men that collected the sperm as an in vitro fertilization backup were less willing to discard the sample (OR = 0.42, 95% CI: 0.18 - 0.97, p = 0.043). CONCLUSIONS: It appears that men's disposition towards post-mortem disposition of their cryopreserved sperm are influenced by their reason for cryopreservation, rather than their age or method used for collection. As cryopreservation has become more common and affordable, understanding the factors that impact men's disposition towards the post-mortem disposition of the cryopreserved gametes is imperative, as this knowledge has the potential to influence institutional policies and legislation, and may help solve future legal conflicts and ethical dilemmas.