RESUMEN
Purpose: The aim of this research is to describe the use of the social media platform, Instagram, by academic ophthalmology residency programs in the United States over time and consider the impact of the COVID-19 pandemic on ophthalmology's social media presence. Methods and Subjects: This cross-sectional study was conducted online by reviewing the publicly accessible Instagram accounts of all accredited US academic ophthalmology residency programs. Main Outcomes and Measures: Number of US ophthalmology residency programs with an affiliated Instagram account were analyzed by year of creation. The content of the top six accounts with the most followers was analyzed by evaluating amount of engagement within defined post categories. Results: Of the 124 ophthalmology residency programs, 78 (62.9%) were identified as having an affiliated Instagram account, 60 accounts (48.4%) were created during the years 2020 or 2021, and 62 (50.0%) accounts focused specifically on promoting the residency training program. Of the top six accounts with the most followers, post categories that received the most engagement were "Medical" and "Group Photo", while those that received the least engagement were "Department Bulletin" and "Miscellaneous." User engagement on posts as measured by likes and comments increased across multiple post categories after January 2020. Conclusion: Social media presence of ophthalmology residency programs on Instagram increased substantially in 2020 and 2021. As a result of the COVID-19 pandemic restricting in-person interactions, residency programs have used alternative platforms to reach applicants. Given the increasing use of such applications, social media will likely continue to become an important aspect of professional engagement in ophthalmology.
RESUMEN
Squamous cell carcinoma in situ (SCCIS) is a prevalent precancerous lesion that can progress to cutaneous squamous cell carcinoma. Although SCCIS is common, its pathogenesis remains poorly understood. To better understand SCCIS development, we performed laser captured microdissection of human SCCIS and the adjacent epidermis to isolate genomic DNA and RNA for next-generation sequencing. Whole-exome sequencing identified UV-signature mutations in multiple genes, including NOTCH1-3 in the epidermis and SCCIS and oncogenic TP53 mutations in SCCIS. Gene families, including SLFN genes, contained UV/oxidative-signature disruptive epidermal mutations that manifested positive selection in SCCIS. The frequency and distribution of NOTCH and TP53 mutations indicate that NOTCH mutations may precede TP53 mutations. RNA sequencing identified 1,166 differentially expressed genes; the top five enriched gene ontology biological processes included (i) immune response, (ii) epidermal development, (iii) protein phosphorylation, (iv) regulation of catalytic activity, and (v) cytoskeletal regulation. The NEURL1 ubiquitin ligase, which targets Notch ligands for degradation, was upregulated in SCCIS. NEURL1 protein was found to be elevated in SCCIS suggesting that increased levels could represent a mechanism for downregulating Notch during UV-induced carcinogenesis. The data from DNA and RNA sequencing of epidermis and SCCIS provide insights regarding SCCIS formation.
Asunto(s)
Carcinoma in Situ/etiología , Carcinoma de Células Escamosas/etiología , Epidermis/efectos de la radiación , Exoma , Perfilación de la Expresión Génica , Neoplasias Inducidas por Radiación/etiología , Neoplasias Cutáneas/etiología , Carcinogénesis/genética , Carcinoma in Situ/genética , Carcinoma de Células Escamosas/genética , Genes p53 , Humanos , Mutación , Neoplasias Inducidas por Radiación/genética , Receptores Notch/genética , Análisis de Secuencia de ARN , Neoplasias Cutáneas/genética , Rayos UltravioletaRESUMEN
Cutaneous squamous cell carcinoma (cSCC) is the second most common form of skin cancer and is associated with cumulative UV exposure. Studies have shown that prolonged voriconazole use promotes cSCC formation; however, the biological mechanisms responsible for the increased incidence remain unclear. Here, we show that voriconazole directly increases oxidative stress in human keratinocytes and promotes UV-induced DNA damage as determined by comet assay, 8-oxoguanine immunofluorescence and mass spectrometry. Voriconazole treatment of human keratinocytes potentiates UV-induced apoptosis and activation of the p38 MAP kinase and 53BP1 UV stress response pathways. The p38 MAP kinase activation promoted by voriconazole exposure can be mitigated by pretreating keratinocytes with N-acetylcysteine. Voriconazole increases oxidative stress in keratinocytes by directly inhibiting catalase leading to lower intracellular NADPH levels and the triazole moieties in voriconazole are critical for inhibiting catalase. Furthermore, voriconazole is shown to promote UV-induced dysplasia in an in vivo model. Together, these data demonstrate that voriconazole potentiates oxidative stress in UV-irradiated keratinocytes through catalase inhibition. Use of antioxidants may mitigate the pro-oncogenic effects of voriconazole.
Asunto(s)
Antifúngicos/farmacología , Daño del ADN/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Rayos Ultravioleta/efectos adversos , Voriconazol/farmacología , 8-Hidroxi-2'-Desoxicoguanosina/metabolismo , Acetilcisteína/farmacología , Animales , Apoptosis/efectos de los fármacos , Apoptosis/efectos de la radiación , Carcinogénesis/efectos de los fármacos , Carcinogénesis/efectos de la radiación , Catalasa/antagonistas & inhibidores , Proliferación Celular/efectos de los fármacos , Células Cultivadas , Daño del ADN/efectos de la radiación , Humanos , Queratinocitos/fisiología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Sistema de Señalización de MAP Quinasas/efectos de la radiación , Ratones , Cultivo Primario de Células , Piel/efectos de los fármacos , Piel/metabolismo , Piel/patología , Piel/efectos de la radiación , Terbinafina/farmacología , Proteína 1 de Unión al Supresor Tumoral P53/metabolismoRESUMEN
Cutaneous squamous cell carcinoma (cSCC) is the second most common cancer in humans, with an incidence of approximately 700,000 cases per year in the United States (Rogers et al., 2010). It is known that cSCC is strongly associated with sun exposure, specifically UVB and UVA, as well as other risk factors, such as human papillomavirus infection, immunodeficiency, and specific medications (Ratushny et al., 2012). However, the precise sequence of biological events leading to tumor development remains unknown. With projected higher incidence of patients with cSCCs in the future, there is a strong need to elucidate the molecular pathways that regulate formation of cSCCs.
RESUMEN
The ocular surface is comprised of the cornea and conjunctiva, which are structures that not only protect the eye but also enable vision. The corneal epithelium is the most superficial layer of the cornea, and therefore first line of defense against external assaults. Damage to this highly specialized structure could lead to vision loss, making it an important structure to investigate and understand. Here, we conducted a search of the current literature on the mechanisms the corneal epithelium has adapted against three frequent insults: UV-radiation, pathogens, and environmental assaults. This review systematically examines the corneal epithelium's response to each assault in order to maintain its role as an invisible shield. The goal of this review is to provide insight into some of the critical functions the corneal epithelium performs that may be valuable to current regenerative studies.
RESUMEN
The American Cancer Society estimates that skin cancer is the most prevalent of all cancers with over 2 million cases of nonmelanoma skin cancer each year and 75,000 melanoma cases in 2012. Representative animal cancer models are important for understanding the underlying molecular pathogenesis of these cancers and the development of novel targeted anticancer therapeutics. In this review, we will discuss some of the important animal models that have been useful to identify important pathways involved in basal cell carcinoma, squamous cell carcinoma, and melanoma.
Asunto(s)
Neoplasias Cutáneas/etiología , Neoplasias Cutáneas/patología , Animales , Carcinoma Basocelular , Carcinoma de Células Escamosas , Modelos Animales de Enfermedad , Humanos , MelanomaRESUMEN
Src family tyrosine kinases (SFK) regulate cell proliferation, and increased SFK activity is common in human carcinomas, including cutaneous squamous cell carcinomas (SCC) and its precursors. The elevated SFK activity in cutaneous SCCs was modeled using K14-Fyn Y528F transgenic mice, which spontaneously form punctate keratotic lesions, scaly plaques, and large tumors resembling actinic keratoses, SCC in situ, and SCCs, respectively. Lesional tissue showed increased levels of activated SFKs, PDK1, STAT3, and ERK1/2, whereas Notch1/NICD protein and transcript levels were decreased. p53 levels also were decreased in SCC in situ and SCCs. Increasing Srcasm levels using a K14-Fyn Y528F/K14-Srcasm double transgenic model markedly inhibited cutaneous neoplasia. In contrast, increased expression of a nonphosphorylatable Srcasm mutant maintained the neoplastic phenotype. Increasing Srcasm levels decreased levels of Fyn, activated SFKs, ERK1/2, PDK1, and phospho-STAT3, and increased Notch1/NICD and p53 levels. Analysis of human specimens revealed that levels of Fyn and activated SFKs were elevated in SCCs compared with adjacent nonlesional epidermis. In addition, Notch1 and Srcasm protein and transcript levels were decreased in human SCCs compared with nonlesional epidermis. Therefore, the SCCs produced by the Fyn Y528F mice resemble their human counterparts at the molecular level. K14-Fyn Y528F mice represent a robust model of cutaneous carcinogenesis that manifests precancerous lesions and SCCs resembling human disease. The Fyn/Srcasm signaling nexus modulates activity of STAT3, PDK1, ERK1/2, Notch1, and p53. Further study of Fyn and Srcasm should provide insights into the mechanisms regulating keratinocyte proliferation and skin carcinogenesis.