Cause Of Melanoma Research Articles

Association between arsenic exposure and melanoma: a meta-analysis.

Melanoma is a highly malignant tumor. Moreover, its prevalence is increasing at a rapid rate year after year. Currently, UV light is the leading cause of melanoma, although numerous other risk factors exist, including arsenic. The link between arsenic and the likelihood of developing melanoma has long been debated. As a result, we conducted a meta-analysis of the available data to investigate the association between arsenic exposure and melanoma. We identified seven non-randomized controlled studies with 41,949 participants by searching the Chinese CNKI, Embase, PubMed, and Cochrane Library databases. We then used random-effects or fixed-effects models to evaluate the pooled odds ratios (OR) and their 95% confidence intervals (CI). Subgroup analyses were also carried out with different included regions. Participants in the study who were exposed to arsenic had a somewhat higher chance of developing melanoma than those who were not (OR = 1.47, 95% CI 1.01-2.13). A subgroup analysis was also carried out for the US region, and the findings were not statistically significant (OR = 1.40, 95% CI 0.94-2.07). This meta-analysis shows that arsenic exposure relates to an increased risk of melanoma.

Melanoma Detection using Deep Learning Algorithms

Abstract: Melanoma is a type of skin cancer that arises from pigment-producing cells called melanocytes. These cells are responsible for the production of melanin, the pigment that gives skin, hair and eyes their color. Melanoma is considered more dangerous than other types of cancer because it can spread (metastasize) to other parts of the body. Key features of melanoma include the formation of abnormal or cancerous cells in the skin pigment. The main cause of melanoma is exposure to ultraviolet (UV) radiation from the sun or tanning beds. Most malignant tumours can be treated if diagnosed early. Therefore, early diagnosis of skin cancer is important to save the lives of patients. With today's technology, skin cancer can be diagnosed early and treated effectively. The traditional method of detecting melanoma relies on eye exams where dermatologists review biopsy results, which is time-consuming. These facilities are less available in rural areas where doctors are often available but dermatologists are not. This study was designed to develop a system that uses deep learning techniques to identify melanoma.

Pesticides and Pollutants associated with Rising Cases of Melanoma

UV radiation is a well-researched cause of malignant melanoma, however more than the sun may be to blame for today’s increased rates of the deadliest form of skin cancer. Pesticides and industrial pollutants are an overlooked yet major causative factor that is still being exposed to ecosystems. This article identifies documented cases of the chemical causes of melanoma stemming from a study that articulates these dangers in the year 2000. It concludes with a message that a clear risk between chemicals and melanoma exists and calls to action the need for mediation.

Assessing the Knowledge, Attitude, Practice towards the Sun Exposure and the use of Sunscreen by the General Population in Makkah, Saudi Arabia

Context: Sunlight exposure is a major cause of melanoma and non-melanoma skin cancer (NMSC). The sunscreen use can reduce the risk of developing melanoma and NMSC. Purpose: To assess the knowledge, attitude, and practice of the general population of Makkah city, Saudi Arabia related to sun exposure and the use of sun protection. Methods and Material: The present study is a descriptive cross-sectional study including 577 participants from the general population of Makkah city, Saudi Arabia using an online pretested Arabic questionnaire designed via Google Forms. Results: More than three-quarters of the respondents (78.4%) stated that sun exposure is harmful; of these, 61.9% stated that tanning, pigmentation, burns, skin cancer, and aging are potential risks that result from sun exposure. Further, 39.5% of the participants sometimes used sunscreen, while 23.9% of them regularly used sunscreen when exposed to the sun; the majority (75.1%) was unaware of the different forms of sunscreens. The factors associated with the regular use of sunscreen were female gender, aged between 18-25 years, and single. The majority of the respondents admitted that sunscreen use is necessary for protection against harmful ultraviolet radiation (88.9%); however, only 34.7% of them used other protective methods such as avoiding exposure to the sun (84.0%) and seeking shade (72.0%). Conclusions: According to the results, various attitudes toward the usage of sunscreen were found. Most of the respondents believed that exposure to the sun are harmful. However, the rate of sunscreen use by our population was average despite their reasonable awareness of the effects of sun exposure. This implies the need for health education campaigns and programs.

Review: The Key Factors to Melanomagenesis.

Melanoma is the most dangerous form of skin cancer that develops from the malignant transformation of the melanocytes located in the basal layer of the epidermis (cutaneous melanoma). Melanocytes may also be found in the meninges, eyes, ears, gastrointestinal tract, genito-urinary system, or other mucosal surfaces (mucosal melanoma). Melanoma is caused by an uncontrolled proliferation of melanocytes, that at first may form a benign lesion (nevogenesis), but in time, it may transition to melanoma, determining what it is named, melanomagenesis. Some tumors may appear spontaneously (de novo melanoma) or on preexisting lesions (nevus-associated melanoma). The exact cause of melanoma may not be fully understood yet, but there are some factors that initiate and promote this malignant process. This study aims to provide a summary of the latest articles regarding the key factors that may lead to melanomagenesis. The secondary objectives are to reveal the relationship between nevi and melanoma, to understand the cause of "de novo" and "nevus-associated melanoma" and highlight the differences between these subtypes.

Gradient differences of immunotherapy efficacy in metastatic melanoma related to sunlight exposure pattern: A population-based study.

Immune checkpoint inhibitors (ICIs) have revolutionized metastatic melanoma (MM) treatment in just a few years. Ultraviolet (UV) in sunlight is the most significant environmental cause of melanoma, which is considered to be the main reason for tumor mutation burden (TMB) increase in melanoma. High TMB usually predicts that PD-1 inhibitors are effective. The sunlight exposure pattern of MM might be a clinical feature that matches TMB. The relationship between sunlight exposure patterns and immunotherapy response in MM is unclear. This study aims to investigate the correlation between sunlight exposure patterns and immunotherapy response in MM and establish nomograms that predict 3- and 5-year overall survival (OS) rate. We searched the Surveillance, Epidemiology, and End Results (SEER) database and enrolled MM cases from 2005-2016. According to the advent of ICIs in 2011, the era was divided into the non-ICIs era (2005-2010) and the ICIs era (2011-2016). Patients were divided into three cohorts according to the primary site sunlight exposure patterns: head and neck in the first cohort, trunk arms and legs in the second cohort, and acral sites in the third cohort. We compared survival differences for each cohort between the two eras, performed stratified analysis, established nomograms for predicting 3- and 5-year OS rate, and performed internal validation. Comparing the survival difference between the ICIs and non-ICIs era, head and neck melanoma showed the greatest improvement in survival, with 3- and 5-year OS rate increasing by 10.2% and 9.1%, respectively (P=0.00011). In trunk arms and legs melanoma, the 3- and 5-year OS rate increased by 4.6% and 3.9%, respectively (P<0.0001). There is no improvement in survival in acral melanoma (AM) between the two eras (P=0.78). The receiver operating characteristic (ROC) curve, area under the ROC curve (AUC) and calibration graphs show good discrimination and accuracy of nomograms. Decision curve analysis (DCA) suggests good clinical utility of nomograms. Based on the classification of sunlight exposure patterns, there is a gradient difference in immunotherapy efficacy for MM. The degree of sunlight exposure is positively correlated with immunotherapy response. The nomograms are sufficiently accurate to predict 3- and 5-year OS rate for MM, allowing for individualized clinical decisions for future clinical work.

Early and accurate detection of melanoma skin cancer using hybrid level set approach.

Digital dermoscopy is used to identify cancer in skin lesions, and sun exposure is one of the leading causes of melanoma. It is crucial to distinguish between healthy skin and malignant lesions when using computerised lesion detection and classification. Lesion segmentation influences categorization accuracy and precision. This study introduces a novel way of classifying lesions. Hair filters, gel, bubbles, and specular reflection are all options. An improved levelling method is employed in an innovative method for detecting and removing cancerous hairs. The lesion is distinguished from the surrounding skin by the adaptive sigmoidal function; this function considers the severity of localised lesions. An improved technique for identifying a lesion from surrounding tissue is proposed in the article, followed by a classifier and available features that resulted in 94.40% accuracy and 93% success. According to research, the best method for selecting features and classifications can produce more accurate predictions before and during treatment. When the recommended strategy is put to the test using the Melanoma Skin Cancer Dataset, the recommended technique outperforms the alternative.

Abstract 2674: Antitumor activity of KIN-2787, a next-generation pan-RAF inhibitor, in preclinical models of human RAF/RAS mutant melanoma

Abstract Background: In the US in 2021, invasive melanoma will account for an estimated 106,000 new cases and &amp;gt; 7,000 deaths. Somatic mutations that activate the MAPK signaling pathway are a leading cause of melanoma with 50% harboring oncogenic BRAF alterations and another 20% with activating NRAS mutations. Of note, NRAS mutant melanoma has been shown to be dependent upon RAF signaling via CRAF dimers for downstream activation of MEK/ERK. While targeted therapies are approved for V600 (Class I, monomer-driven) BRAF mutant melanoma, no approved targeted therapy exists for patients with melanoma driven by Class II or Class III dimer-dependent BRAF alterations or NRAS mutations. KIN-2787 is a novel, orally available, potent, and selective pan-RAF inhibitor designed to be effective in RAF-dependent cancers, including all classes of BRAF alterations, by targeting mutant BRAF monomers and RAF dimers, regardless of isoform. Methods: KIN-2787 activity was assessed by suppression of downstream MAPK pathway signaling and subsequent cell growth inhibition in a panel of human melanoma cell lines. In vivo KIN-2787 efficacy was evaluated in BRAF and NRAS mutant melanoma cell- and patient-derived xenograft models. Results: KIN-2787 cellular activity was measured by inhibition of ERK phosphorylation across a panel of melanoma cell lines, including those harboring Class I BRAF alterations, Class II and III BRAF alterations, NRAS mutations, KRAS mutations, and wild type RAF/RAS. In contrast to vemurafenib, an approved BRAF inhibitor with activity limited to Class I BRAF alterations, KIN-2787 was active across all classes of BRAF mutant melanoma cells (EC50 values &amp;lt; 100 nM). NRAS and KRAS mutant cell lines were moderately responsive to KIN-2787 inhibition. Melanoma cells expressing wild type RAS/RAF were the least sensitive to MAPK pathway inhibition by KIN-2787. KIN-2787 also inhibited cell proliferation in BRAF and NRAS mutant melanoma in 2D and 3D cell cultures. Daily KIN-2787 treatment resulted in significant tumor growth inhibition in human melanoma xenograft models bearing Class I, II and III BRAF alterations as well as NRAS mutations and was associated with MAPK pathway suppression. Additionally, KIN-2787 was efficacious in a pre-/post-treatment melanoma PDX pair in which the original tumor was Class I BRAF V600E but acquired a Class II BRAF kinase domain duplication upon progression on dabrafenib + trametinib. Details from the above findings will be presented at the meeting. Conclusions: KIN-2787 is a next-generation, pan-RAF inhibitor with in vitro and in vivo activity against human melanoma driven by BRAF and/or NRAS mutations. Data supports KIN-2787 use in acquired BRAF dimer-dependent resistance to BRAF+MEK inhibitor therapy. A Phase I dose escalation and expansion clinical trial evaluating the safety and efficacy of KIN-2787 is ongoing (NCT04913285). Citation Format: Nichol L. G. Miller, Tim S. Wang, Paul Severson, Ping Jiang, Michelle Perez, Noel Timple, Toufike Kanouni, Aleksandra Franovic, Eric S. Martin, Eric Murphy. Antitumor activity of KIN-2787, a next-generation pan-RAF inhibitor, in preclinical models of human RAF/RAS mutant melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2022; 2022 Apr 8-13. Philadelphia (PA): AACR; Cancer Res 2022;82(12_Suppl):Abstract nr 2674.

Cutaneous malignant melanoma incidence is strongly associated with European depigmented skin type regardless of ambient ultraviolet radiation levels: evidence from Worldwide population-based data.

Current public health advice is that high ultraviolet radiation (UVR) exposure is the primary cause of Malignant Melanoma of skin (CMM), however, despite the use of sun-blocking products incidence of melanoma is increasing. To investigate the UVR influence on CMM incidence worldwide WHO, United Nations, World Bank databases and literature provided 182 country-specific melanoma incidence estimates, daily UVR levels, skin colour (EEL), socioeconomic status (GDP PPP), magnitude of reduced natural selection (Ibs), ageing, urbanization, percentage of European descendants (Eu%), and depigmentation (blonde hair colour), for parametric and non-parametric correlations, multivariate regressions and analyses of variance. Worldwide, UVR levels showed negative correlation with melanoma incidence (“rho” = −0.515, p < 0.001), remaining significant and negative in parametric partial correlation (r = −0.513, p < 0.001) with other variables kept constant. After standardising melanoma incidence for Eu%, melanoma correlation with UVR disappeared completely (“rho” = 0.004, p = 0.967, n = 127). The results question classical views that UVR causes melanoma. No correlation between UVR level and melanoma incidence was present when Eu% (depigmented or light skin type) was kept statistically constant, even after adjusting for other known variables. Countries with lower UVR levels and more Eu% (depigmented or light skin people) have higher melanoma incidence. Critically, this means that individual genetic low skin pigmentation factors predict melanoma risk regardless of UVR exposure levels, and even at low-UVR levels.

26419 Rainfall associated with increased melanoma among non-Hispanic whites

The major environmental cause of melanoma is likely solar ultraviolet radiation (UVR). Thus, modifiers of UVR, such as rainfall and its associated cloud cover, have the potential to impact melanoma incidence. While prior research theorizes decreased rainfall may be associated with increased melanoma as drier weather encourages outdoor activity in climate change scenarios, this research may suggest otherwise. The authors obtained county-level melanoma incidence data from the National Cancer Institute’s Surveillance, Epidemiology, and End Results (SEER) Program and rainfall data from the National Oceanic and Atmospheric Association (NOAA) while controlling for age, race, ethnicity, income, latitude, altitude, and other UVR influencers.

Genetic counseling and testing for hereditary causes of melanoma can lead to earlier detection of skin cancer and other malignancies

International Journal of DermatologyVolume 61, Issue 6 p. e233-e234 Correspondence Genetic counseling and testing for hereditary causes of melanoma can lead to earlier detection of skin cancer and other malignancies Albert E. Zhou PhD, Corresponding Author Albert E. Zhou PhD albert.zhou@som.umaryland.edu University of Maryland School of Medicine, Baltimore, MD, USASearch for more papers by this authorKarl M. Hoegler MD, Karl M. Hoegler MD University of Maryland School of Medicine, Baltimore, MD, USASearch for more papers by this authorJulie F. Solimine MGC, CGC, Julie F. Solimine MGC, CGC University of Maryland School of Medicine, Baltimore, MD, USASearch for more papers by this author Albert E. Zhou PhD, Corresponding Author Albert E. Zhou PhD albert.zhou@som.umaryland.edu University of Maryland School of Medicine, Baltimore, MD, USASearch for more papers by this authorKarl M. Hoegler MD, Karl M. Hoegler MD University of Maryland School of Medicine, Baltimore, MD, USASearch for more papers by this authorJulie F. Solimine MGC, CGC, Julie F. Solimine MGC, CGC University of Maryland School of Medicine, Baltimore, MD, USASearch for more papers by this author First published: 17 June 2021 https://doi.org/10.1111/ijd.15716 Conflict of interest: None. Funding source: None. Reprint requests: Albert Zhou, PhD. Read the full textAboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onFacebookTwitterLinked InRedditWechat No abstract is available for this article. Volume61, Issue6June 2022Pages e233-e234 RelatedInformation

A study looking at UV exposure and genetic risks in relation to melanoma

British Journal of DermatologyVolume 183, Issue 2 p. e39-e39 Plain Language Summary Free Access A study looking at UV exposure and genetic risks in relation to melanoma First published: 02 August 2020 https://doi.org/10.1111/bjd.19273 AboutPDF ToolsRequest permissionExport citationAdd to favoritesTrack citation ShareShare Give accessShare full text accessShare full-text accessPlease review our Terms and Conditions of Use and check box below to share full-text version of article.I have read and accept the Wiley Online Library Terms and Conditions of UseShareable LinkUse the link below to share a full-text version of this article with your friends and colleagues. Learn more.Copy URL Share a linkShare onEmailFacebookTwitterLinked InRedditWechat Abstract Melanomas are common cancers among people of European ancestry, accounting for 1·6% of all new cancer cases and 0·6% of all cancer deaths worldwide in 2018. The only environmental factor consistently implicated as a cause of melanoma is ultraviolet (UV) radiation, but the relationship is complex, and little is known about how genetic factors influence the association between UV and melanoma. The effects of UV exposure are affected by ‘host factors’ (meaning factors that are specific to the individual, such as their genes), and by ‘host behaviours’ (such as their patterns of sun exposure and history of sunburns). The aim of this study was to examine whether melanoma risk varies according to reported levels of sun exposure, even within populations exposed to year-round high levels of sunlight (i.e. Queensland, Australia). More particularly, the authors sought to determine whether the associations with sunlight differ according to a person's inherent genetic risk. In a large Australian study, country of birth, age at migration and sunburns during all periods of life were all strongly associated with melanoma risk. People who had a past history of other types of skin cancer (specifically, BCC or SCC) and of other skin lesions caused by sun exposure had a higher risk of developing melanoma than people without sun-related skin lesions. The authors found evidence for gene-environment interactions that are consistent with the ‘divergent pathway’ hypothesis for melanoma development, which almost 20 years ago proposed that people with a high genetic susceptibility (i.e. at higher risk of melanoma, genetically) may only need modest levels of sun exposure to trigger melanoma development, whereas those with low genetic susceptibility require continued high levels of sun exposure to trigger melanoma development. In line with this hypothesis, the authors found that people who were at low genetic risk for melanoma, but who did eventually develop melanoma, were more likely to have been treated for sun-related skin lesions than people at high genetic risk. In other words, the people at low genetic risk who developed melanoma appeared to need a much larger dose of sun exposure than those at high genetic risk. In contrast, among people at high genetic risk, markers of high-level early life ambient exposure were relatively more important. These findings may help to identify and inform people at high risk of melanoma who stand to benefit most from adopting sun protective behaviours. Linked Article: Olsen et al. Br J Dermatol 2020; 183:303–310. Volume183, Issue2August 2020Pages e39-e39 RelatedInformation

Analysis of Melanoma Lesion Images using Feature Extraction &amp; Classification Algorithms

Among the most dangerous of cancers found in human beings, skin cancer is the prevalent one. These are of various forms. The most sporadic among them is melanoma. Early phase identification of melanoma will be helpful in curing it. Intensive skin exposure to UV radiation is the principal cause of melanoma. In this article, along with other techniques for extracting features (LDP [Local Directional Patterns], LBP [Local Binary Patterns], Convolutional Neural Networks [CNN]), we have used an SVM classifier for the study of melanoma skin photos. Such suggested algorithms are best graded when opposed to other recognition schemes. The LBP and LDP gives us means to extract features; these figures are subsequently used for identification of derived features from these methods or algorithms and classified or separated by the SVM (Support Vector Machine) classifier. For many of the classifications of melanoma skin images using these algorithms, we have accuracy nearly above 80 %, whereby the LBP system together with the SVM classifier was the most powerful attribute extraction tool of the three with their polynomial kernel type. Thus using this algorithm-classifier, the melanoma skin lesion images can be detected and diagnosed by the doctors in its early stage itself, resultantly, helping save lives.

Cell cycle regulatory markers in melanoma: New strategies in diagnosis and treatment.

Background: Melanoma has been known as an aggressive type of skin cancer in recent years. Reports have distributed the spread rate of melanoma among white skin populations. Also, many studies have mentioned several causes of melanoma. Ultraviolet radiation was represented to be the most important reason for occurrence of melanoma. However, recent studies have found that a combination of factors, such as environmental and genetic factors, can contribute to occurrence of various cancers, specifically melanoma. Methods: Different studies have been conducted on the efficacy of genetic disorders in melanoma. These surveys marked the key role of specific biomarkers in molecular and cellular processes, and investigations have found the expression of several genes in these processes. In addition, aberrant expression of these genes due to mutation and methylation can affect the whole process. Results: The expression process of these genes is regulated by microRNAs. These new biomolecules have been considered as negative regulators because of managing molecular and cellular processes. MicroRNAs are small conserved regulators attached to their targets leading to rearrangement of gene expression. Adherence of these noncoding RNAs can cause mRNA degradation or inhibit its translation. Conclusion: Recently, the application of specific genes in melanoma has been studied. In this review, the way melanoma is regulated because of these biomarkers and their demand through cell cycle in diagnosis, prognosis, and therapeutic periods was considered. Keywords: Melanoma, Biomarkers, Cell cycle, Biomolecules

Melanoma and skin cancers in airline pilots and cabin crew

Ultraviolet radiation (UVR) from the sun is a major cause of skin cancer, including melanoma which is the most deadly form of the disease. As part of their jobs, airline pilots and cabin crews are exposed to cosmic radiation, and airline pilots may receive UVR on the flight deck, potentially resulting in skin cancer. The authors, based in Australia and the U.K, therefore systematically reviewed all relevant studies to find out risk of, and mortality (death) from, melanoma and other skin cancers in airline pilots and cabin crews. The majority of the 12 studies identified were conducted in the 1970s to 1990s in Europe or North America. They found that melanoma and other skin cancers were around twice as common in pilots and cabin crews as in the general community. Melanoma deaths were also doubled in the pilots but not in the aircrew. Ultraviolet B radiation from the sun is the main cause of melanoma and other skin cancer, but ultraviolet B radiation is not detectable or not increased above ground level values in modern airline cabins and flight decks. Also occupational levels of cosmic radiation among pilots and cabin crew are assessed not to be hazardous. However, high recreational sun exposure (i.e. time in the sun when not working) among airline pilots and cabin crews cannot be ruled out, especially in the existing published studies reflecting sun exposure patterns of previous decades. The authors concluded that airline pilots’ and cabin crews’ high risk of melanoma and other skin cancers could not be clearly attributed to occupational (job related) factors. They called for up‐to‐date studies of the topic.

Isolated Metastatic Malignant Melanoma of the Right Inguinal Lymph Node with Unknown Primary Lesion

Malignant melanoma develops from the pigment containing cells known as melanocytes. Melanoma is more common in men than in women. It is found typically in the skin. It is also found in the mouth, intestine, eye and other sites. Melanoma may develop from a mole with changes including an increasing in size, irregular edges, changes in color, itchiness or skin breakdown. Prognosis is poor if it is not treated early. The primary cause of melanoma is UV light exposure. Patients with history of affected family members and poor immune function are at greater risk. Diagnosis is by biopsy from any affected skin lesion. Recurrence is common even many years after the initial diagnosis. Here we present a case of malignant melanoma of the inguinal lymph node with unknown primary lesion. Surgery was done with complete excision of inguinal lymph node. Biopsy report showed metastatic malignant melanoma.J Enam Med Col 2018; 8(3): 174-176

BRCA1/2 mutations are not a common cause of malignant melanoma in the Polish population.

The association of BRCA1/2 mutations with melanoma is not completely determined; the interpretation of variants of unknown significance is also problematic. To evaluate these issues we explored the molecular basis of melanoma risk by performing whole-exome sequencing on a cohort of 96 unrelated Polish early-onset melanoma patients and targeted sequencing of BRCA1/2 genes on additional 30 melanoma patients with familial aggregation of breast and other cancers. Sequencing was performed on peripheral blood. We evaluated MutationTaster, Polyphen2, SIFT, PROVEAN algorithms, analyzed segregation with cancer disease (in both families with identified BRCA2 variants) and in one family performed LOH (based on 2 primary tumors). We found neither pathogenic mutations nor variants of unknown significance within BRCA1. We identified two BRCA2 variants of unknown significance: c.9334G>A and c.4534 C>T. Disease allele frequency was evaluated by genotyping of 1230 consecutive melanoma cases, 5000 breast cancer patients, 3500 prostate cancers and 9900 controls. Both variants were found to be absent among unselected cancer patients and healthy controls. The MutationTaster, Polyphen2 and SIFT algorithms indicate that c.9334G>A is a damaging variant. Due to lack of tumour tissue LOH analysis could not be performed for this variant. The variant segregated with the disease. The c.4534 C>T variant did not segregate with disease, there was no LOH of the variant. The c.9334G>A variant, classified as a rare variant of unknown significance, on current evidence may predisposes to cancers of the breast, prostate and melanoma. Functional studies to describe how the DNA change affects the protein function and a large multi-center study to evaluate its penetrance are required.

Visual Cancer Communication on Social Media: An Examination of Content and Effects of #Melanomasucks.

BackgroundInstagram is increasingly becoming a platform on which visual communication of cancer takes place, but few studies have investigated the content and effects. In particular, a paucity of research has evaluated the effects of visual communication of cancer on participative engagement outcomes.ObjectiveThe objective of our study was to investigate cancer-related beliefs and emotions shared on Instagram and to examine their effects on participative engagement outcomes including likes, comments, and social support.MethodsThis study analyzed the content of 441 posts of #melanomasucks on Instagram and assessed the effects of the content characteristics on outcomes, including the number of likes and comments and types of social support using group least absolute shrinkage and selection operator logistic regression.ResultsPosts about controlling melanoma were most frequent (271/441, 61.5%), followed by 240 (54.4%) posts about outcomes of having melanoma. Ninety posts (20.4%) were about the causes of melanoma. A greater number of posts expressed positive (159/441, 36.1%) than negative emotions (100/441, 22.7%). Eighty posts (18.1%) expressed hope, making it the most frequently expressed emotion; 49 posts expressed fear (11.1%), 46 were humorous (10.4%), and 46 showed sadness (10.4%). Posts about self behavior as a cause of melanoma decreased likes (P<.001) and social support comments (P=.048). Posts about physical consequences of melanoma decreased likes (P=.02) but increased comments (P<.001) and emotional social support (P<.001); posts about melanoma treatment experience increased comments (P=.03) and emotional social support (P<.001). None of the expressions of positive emotions increased likes, comments, or social support. Expression of anger increased the number of likes (P<.001) but those about fear (P<.001) and joy (P=.006) decreased the number of likes. Posts about fear (P=.003) and sadness (P=.003) increased emotional social support. Posts showing images of melanoma or its treatment on the face or body parts made up 21.8% (96/441) of total posts. Inclusion of images increased the number of comments (P=.001).ConclusionsTo our knowledge, this is the first investigation of the content and effects of user-generated visual cancer communication on social media. The findings show where the self-expressive and social engagement functions of #melanomasucks converge and diverge, providing implications for extending research on the commonsense model of illness and for developing conceptual frameworks explaining participative engagement on social media.

Abstract 3323: Role of RNA methyltransferase METTL3 in melanoma

Abstract Melanoma is the sixth most common cancer in the USA. Introduction of BRAF inhibitors and advances in cancer immunotherapy has greatly improved treatment of melanoma, however, the problem of tumour relapse and therapy resistance persists. Better understanding of the mechanism of development of the diseases is urgently needed to improve therapeutic intervention. Role of DNA and histone modifications have been well established in several diseases, however, RNA modifications, specifically, N6 methyl adenosine (m6A), has only recently begun to be shown to play critical role in cancer. m6A plays crucial roles in mRNA stability, splicing, export, translation and decay and is regulated by: methyltransferase complex proteins METTL3, METTL14, and WTAP; the demethylases FTO and ALKBH5, and the m6A reader proteins. In the present study, we uncover the role of RNA methyltransferase METTL3 in human melanoma cells. METTL3 expression was assessed in 8 melanoma cell lines (A375, A375MA2, A2058, WM164, 451Lu, WM793, SKMEL2, WM3918). Western blotting data revealed METTL3 to be upregulated in seven melanoma cell lines (except A2058) relative to normal melanocytes. To uncover the role of METTL3 in melanoma, we knockdown METTL3 with lentiviral shRNA and studied the effect on melanoma cells tumorigenesis. The colony formation assay revealed reduced colony number in the METTL3 knockdown A375, A375MA2 and WM793 cells relative to the scrambled control cells. The main cause of melanoma associated fatality is its metastatic dissemination we therefore, next sought to investigate whether METTL3 could affect melanoma cells migration and invasiveness. We performed migration and invasion assays to detect the migratory potential of control or METTL3 knockdown A375, A375MA2 and WM793 cells. Interestingly, both migration and invasion was found to be reduced in METTL3 knockdown cells in all the three cell lines examined. RNA dot blot assay demonstrated a decreased m6A level in total RNA of the METTL3 knockdown cells relative to control cells. p16 and p53 mRNA were found to be enriched in m6A immunoprecipitated samples as compared to IgG control, pointing towards a potential role of m6A in regulating expression of melanoma associated genes. Ongoing effort is aimed at identifying what known or novel regulators of the migratory/invasive cascade is regulated by METTL3 and whether it is through m6A mediated or independent mechanisms. In summary, we have shown that METTL3 is overexpressed in human melanoma and play an important role in metastasis. Citation Format: Ujwal Dahal, Kang Le, Mamta Gupta. Role of RNA methyltransferase METTL3 in melanoma [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr 3323.

Abstract LB-355: Loss of keratinocyte desmoglein 1 occurs during melanoma development and alters crosstalk between keratinocytes and melanocytes

Abstract Ultraviolet (UV)-induced mutations in melanocytes are a well-established cause of melanoma. However, histologically normal “fields” of altered keratinocytes present in sun-exposed epidermis could also drive initiation and progression of melanoma. We previously demonstrated that UV radiation reduced expression of the keratinocyte desmosomal cadherin, desmoglein 1 (Dsg1), and that loss-of-function mutations in Dsg1 increased keratinocyte cytokine production in Severe dermatitis, multiple Allergies, and Metabolic wasting (SAM) syndrome. Based on these observations we hypothesized that loss of Dsg1 alters the microenvironment through increased cytokine signaling. Here, we show that Dsg1 expression is progressively reduced in regions surrounding human dysplastic nevi, melanoma in situ, and stage I/II melanomas. In contrast, keratinocyte E-cadherin was not significantly altered in early tumors. Dsg1 knockdown in keratinocytes in vitro increased phospho-EGFR, phospho-Stat3, and nuclear NFκB, while increasing keratinocyte mRNAs encoding IL-1α, IL-1β, IL-6 and IL-8 pro-inflammatory cytokines. Re-expressing silencing-resistant Dsg1 returned cytokine levels to control levels. To determine whether Dsg1 loss in keratinocytes elicits paracrine-mediated changes in melanocyte behavior, we treated normal primary melanocytes with conditioned media from Dsg1-silenced keratinocytes. Short-term (overnight) exposure to Dsg1-deficient conditioned media resulted in significantly increased melanocyte dendrite length, similar to morphology changes induced by UV exposure; however, long-term (7 day) exposure resulted in significantly shorter dendrites. Melanocytes exposed to Dsg1-deficient media increased melanin secretion and decreased melanin retention, a phenomenon associated with the process of transformation. Melanocytes incorporated into Dsg1-deficient 3D human skin equivalents exhibited aberrant behavior, including increased numbers and mis-localization to suprabasal layers. Based on these observations, we propose that under homeostatic conditions Dsg1 functions to maintain baseline levels of cytokine signaling, but that Dsg1 loss due to environmental stress disrupts keratinocyte:melanocyte communication through altered paracrine signaling to promote melanoma initiation. Citation Format: Christopher Arnette, Jodi L. Johnson, Hope E. Burks, Jennifer L. Koetsier, Kathleen J. Green. Loss of keratinocyte desmoglein 1 occurs during melanoma development and alters crosstalk between keratinocytes and melanocytes [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2018; 2018 Apr 14-18; Chicago, IL. Philadelphia (PA): AACR; Cancer Res 2018;78(13 Suppl):Abstract nr LB-355.