Development Of Skin Cancer Research Articles

Beta Human Papillomavirus 8 E6 Induces Micronucleus Formation and Promotes Chromothripsis.

Cutaneous beta genus human papillomaviruses (β-HPVs) are suspected to promote the development of nonmelanoma skin cancer (NMSC) by destabilizing the host genome. Multiple studies have established the genome destabilizing capacities of β-HPV proteins E6 and E7 as a cofactor with UV. However, the E6 protein from β-HPV8 (HPV8 E6) induces tumors in mice without UV exposure. Here, we examined a UV-independent mechanism of HPV8 E6-induced genome destabilization. We showed that HPV8 E6 reduced the abundance of anaphase bridge resolving helicase, Bloom syndrome protein (BLM). The diminished BLM was associated with increased segregation errors and micronuclei. These HPV8 E6-induced micronuclei had disordered micronuclear envelopes but retained replication and transcription competence. HPV8 E6 decreased antiproliferative responses to micronuclei and time-lapse imaging revealed HPV8 E6 promoted cells with micronuclei to complete mitosis. Finally, whole-genome sequencing revealed that HPV8 E6 induced chromothripsis in nine chromosomes. These data provide insight into mechanisms by which HPV8 E6 induces genome instability independent of UV exposure. IMPORTANCE Some beta genus human papillomaviruses (β-HPVs) may promote skin carcinogenesis by inducing mutations in the host genome. Supporting this, the E6 protein from β-HPV8 (8 E6) promotes skin cancer in mice with or without UV exposure. Many mechanisms by which 8 E6 increases mutations caused by UV have been elucidated, but less is known about how 8 E6 induces mutations without UV. We address that knowledge gap by showing that 8 E6 causes mutations stemming from mitotic errors. Specifically, 8 E6 reduces the abundance of BLM, a helicase that resolves and prevents anaphase bridges. This hinders anaphase bridge resolution and increases their frequency. 8 E6 makes the micronuclei that can result from anaphase bridges more common. These micronuclei often have disrupted envelopes yet retain localization of nuclear-trafficked proteins. 8 E6 promotes the growth of cells with micronuclei and causes chromothripsis, a mutagenic process where hundreds to thousands of mutations occur in a chromosome.

Frequency of skin cancer and evaluation of risk factors: A hospital-based study from Turkey.

Skin cancers are the most common type of cancer with a significantly increasing incidence. The purpose of the study was to uncover the one-year frequency of melanoma and non-melanoma skin cancers (NMSC) and to determine the risk factors in the development of skin cancer. The study included 7396 people from all age groups admitted to the dermatology clinic between October 2020 and 2021. The sociodemographic characteristics, sun protection habits, chronic diseases, and drug and vitamin use were evaluated. Lesions with clinical suspicion of skin cancer were excised. The frequency of skin cancer was found to be 2.7%, basal cell cancer (BCC) 1.2%, squamous cell cancer (SCC) 1.1%, malignant melanoma (MM) was 0.4%. Daily black tea consumption was found to be a risk factor for three type of skin cancer, BCC (p=0.021), SCC (p=0.006), and MM (p=0.002), respectively. Obesity was observed as a risk factor for BCC (p=0.005) and MM (p=0.008). We found that having a history of alcohol use were an independent risk factor for all skin cancer types and BMI <30 for SCC. Vitamin D and supplemental drugs intake were observed as protective factors for BCC (p=0.035, p=0.007, respectively). Daily coffee consumption was determined as a protective factor for SCC (p < 0.001) and MM (p=0.049). This study estimates the frequency of NMSC and melanoma. Also provides evidence to determine the risk factors and probably protective factors for the development of skin cancers.

Developing skin cancer education materials for darker skin populations: crowdsourced design, message targeting, and acral lentiginous melanoma.

Despite decreased susceptibility, darker skin individuals who develop melanoma have worse survival. This disparity in melanoma mortality is the largest for any cancer, and partly driven by a lack of patient education materials targeted to darker skin populations in whom acral lentiginous melanoma (ALM) is the most common subtype. To address this communication disparity, the current study reports a multi-phase design process that leverages crowdsourcing and message testing to develop ALM-focused patient education materials for darker skin populations. Crowdsourced design was utilized to develop a pool of designs (phase 1), the pool was narrowed and thematically analyzed (phase 2), and select designs were evaluated via a message experiment (N = 1877). For darker skin populations, designs that depicted people enhanced knowledge of ALM through message memorability. The current study engages melanoma disparities by providing ALM patient education materials for darker skin populations vetted via a multi-phase process.

Prevalence and determinants of sunburns and sun protection behaviors among children: A nationwide cross-sectional survey in Switzerland

BACKGROUND: High exposure to solar ultraviolet radiation in early life increases the risk of developing skin cancer later, with increasing risk related to an increasing number of sunburns. Switzerland has high incidence rates of skin cancer compared to surrounding countries. We aimed to estimate the prevalence of sunburns and sun protection behaviors and their potential determinants among children in Switzerland. METHODS: In February 2019, we sent questionnaires to the parents of a random sample of 8,221 Swiss resident children. The questionnaires of 2,841 children were returned (response rate 35%). In spring and summer of the same year, follow-up questionnaires were sent to these children (response rate ~50%). Parents were asked about their child regarding protection measures, number of sunburns in the previous year, and skin phototype. We calculated the prevalence of sunburns and sun-protective behaviors (wearing a hat, seeking for shade, and use of sunscreen) by season, sociodemographic characteristics and skin phototype. RESULTS: Among participating children, 39.9% had at least one sunburn in the previous year, of whom 20.5% had a severe sunburn. When outside on a sunny day, 50.3% of the children wore a hat in summer (46.8% in spring), 21.1% (19.8%) sought shade more than half of the time, and 53.6% (43.5%) wore sunscreen. Prevalence of sunburns and of severe sunburns was higher among older children, boys, and children with sensitive skin. Protective measures were more frequent among younger children, girls, and children with sensitive skin. Prevalence of both outcomes varied substantially between regions. Sunburn prevalence was associated with lower use of sun protection. CONCLUSIONS: Compared to previous regional studies in Switzerland, we found a lower prevalence of sunburns and of protection behaviors, with important regional heterogeneity. Our results should help tailor sun exposure prevention measures to specific age groups and regions. KEYWORDS : sunburn, children, skin cancer

Do sunscreens have more positive or negative effects? Study review

Introduction: UV radiation is related to skin cancers, skin photoaging and sunburn. It can be harmful for human skin, so it is crucial to have a protection against sun rays. Substances protecting people from sun are sunscreens, that block and absorb UV radiation. The first sunscreen was discovered in 1928 and, since then, there have been many concerns about its safety, efectiveness and impant on the environment. Types of accessible sunscreens are physical sunscreens, chemical sunscreens and a combination. This study review is performed to assess possible risks of using sunscreens and evaluate if there are more positive or negative effects of their action. The aim of the study: To evaluate positive and negative effects of sunscreens action. Materials and methods: We searched Pubmed and ResearchGate in order to find relevant studies about sunscreens and their impact on human skin, human health and environment. Results: There seem to be some adverse effects of sunblockers for the environment, such as destroying coral reefs, bioaccumulating in fish tissue and water sources. In some studies there was mentioned a negative impact of sunscreens on hormonal systems and pregnancy, as well as on human skin. On the other hand, many studies display that sunblockers inhibit the carcinogenic effect of sun rays, preventing people from developing skin cancers. Conclusions: Althought sunscreens can have some negative effects, studies showed that there are more positive effects of their action. They can be harmful for the environment, but at the same time they can be a protection. Sunscreens protect skin from developing skin cancer and also delay skin aging. However, the protection against sun is complex.

Skin cancer in essential thrombocythaemia and polycythaemia vera patients treated with hydroxycarbamide.

Hydroxycarbamide (HC) is used as a cytoreductive treatment in myeloproliferative neoplasms (MPN). Observational studies have raised the possibility that HC contributes to the development of secondary malignancies, including skin tumours in MPN patients. In this retrospective observational study, we report a single-centre experience of 324 HC-treated MPN patients with long-term follow-up, compared to 47 MPN patients not on HC. Thirty-three patients (10.2%) (HC) versus one patient (2.1%) (no HC) developed skin tumours during follow-up (Hazard ratios [HR] 5.70, 95% confidence intervals 0.66-48.09, p=0.112). However, male gender, age at MPN diagnosis, type of MPN (polycythaemia rubra vera) and previous history of skin cancer were prognostic variables associated with development of skin cancer.

34244 Acquired epidermodysplasia verruciformis: A retrospective review of cases

Epidermodysplasia verruciformis is a rare genodermatosis characterized by an unusual susceptibility to the beta genus of the human papillomavirus and early development of skin cancers. Acquired epidermodysplasia verruciformis (AEDV) is a distinct rare disorder with similar clinical and histopathologic manifestation, strongly associated with immunosuppression. Clinical course, therapeutic management, and potential for skin cancer development in AEDV is largely unknown. We report 7 patients with AEDV diagnosed between January 1992 and November 2019. Four patients were males (57.1%), with median age of diagnosis of 29 years, range 9-67 years. All patients had underlying immunodeficiency; 5 with acquired immunodeficiencies (HIV/AIDS, heart transplant, kidney transplant, pancreas transplant, systemic lupus erythematosus and Crohn’s disease) and 2 with congenital immunodeficiencies (isolated CD4 lymphopenia and immunodeficiency 71 with inflammatory disease and congenital thrombocytopenia). For patients with acquired immunodeficiencies, the median interval between the onset of immunosuppression and the presentation of AEDV lesions was 5 years, range 3-7 years. Patients were followed for a median of 5.5 years, range 1-10 years. Only 1 patient (14.2%) progressed to develop squamous cell carcinoma of the left forearm. Topical imiquimod (3/7), topical tretinoin (3/7), cryotherapy (2/7), intralesional candida injection (2/7), and topical podophyllotoxin (1/7) were attempted for treatment of AEDV. Partial resolution of AEDV lesions was observed with intralesional candida injection (2/2) and topical retinoid (1/3). Initiation of HAART yielded complete resolution in one patient with HIV/AIDS. In conclusion, we report a series of AEDV with emphasis on therapeutic management, clinical course, and long-term follow up of this rare disorder.

33632 Educational interventions may improve sun protection and skin cancer awareness in outdoor occupational workers

Introduction: Skin cancer is a preventable, yet leading, cause of cancer in the United States. Outdoor workers experience more UV exposure and report lower rates of sunscreen use. As such, they are at increased risk of developing skin cancer without intervention. Sun protection education, a means of preventative intervention, is associated with increased use of sun protective measures in several populations.

34516 Top selling pediatric sunscreens: An analysis of prices, claims, and allergens

Introduction: Childhood sun exposure is associated with subsequent skin cancer development. Herein, we analyze the characteristics of top-selling pediatric sunscreens and evaluate prices, marketing claims, and allergens.

Combined Kdm6a and Trp53 Deficiency Drives the Development of Squamous Cell Skin Cancer in Mice

Cutaneous squamous cell carcinoma (cSCC) has among the highest mutation burdens of all cancers, reflecting its pathogenic association with the mutagenic effects of UV light exposure. Although mutations in cancer-relevant genes such as TP53 and NOTCH1 are common in cSCC, they are also tolerated in normal skin and suggest that other events are required for transformation; it is not yet clear whether epigenetic regulators cooperate in the pathogenesis of cSCC. KDM6A encodes a histone H3K27me2/me3 demethylase that is frequently mutated in cSCC and other cancers. Previous sequencing studies indicate that roughly 7% of cSCC samples harbor KDM6A mutations, including frequent truncating mutations, suggesting a role for this gene as a tumor suppressor in cSCC. Mice with epidermal deficiency of both Kdm6a and Trp53 exhibited 100% penetrant, spontaneous cSCC development within a year, and exome sequencing of resulting tumors reveals recurrent mutations in Ncstn and Vcan. Four of 16 tumors exhibited deletions in large portions of chromosome 1 involving Ncstn, whereas another 25% of tumors harbored deletions in chromosome 19 involving Pten, implicating the loss of other tumor suppressors as cooperating events for combined KDM6A- and TRP53-dependent tumorigenesis. This study suggests that KDM6A acts as an important tumor suppressor for cSCC pathogenesis.

Skin cancer and DNA mutation due to ultraviolet radiation

&lt;p&gt;Ultraviolet (UV) radiation is emitted by the Sun as well as man-made sources such as tanning beds and welding torches. The process of energy being emitted from any source is known as radiation which can take many different forms, from extremely high-energy radiation like X-rays and gamma rays to extremely low-energy radiation like radio waves. UV photons are in the middle of the electromagnetic spectrum. They have higher energy than visible light but a lower energy than X-rays. It is divided into numerous groups based on the amount of energy they contain. Higher-energy UV photons are included in ionizing radiation, which means they have enough energy to ionize an atom or molecule. Ionizing radiation can cause cancer by damaging a cell's DNA; however, it doesn’t have enough energy to penetrate deep into the body, thus it mainly effects the skin only. UV radiations are considered the most carcinogenic factors which leads to skin cancer. Over $50 million each year is estimated to treat the melanoma skin cancer, but the incidences kept rising each year. The tanning and pigmentation in the skin are the main factors to develop skin cancer that rise concerns about ozone depletion. Continuing research should contribute to an improved knowledge of the genetic and immune suppressive mechanisms involved in the role of the tumor suppressor. Research into skin cancer may help raise consciousness about the harmful effects of UV which leads to improved methods of prevention and treatment of skin cancer.&lt;/p&gt;

A convolutional neural network based system for detection of actinic keratosis in clinical images of cutaneous field cancerization

Areas of cutaneous field cancerization (CFC) occur in sun-damaged skin and are prone to skin cancer development. Actinic keratosis (AK) is the pathognomonic lesion of CFC. Therefore, the reliable and non-invasive AK burden assessment is essential to assist clinicians in delivering patient-tailored therapeutic interventions and support the objective evaluation of emerging therapeutic modalities. Herein, we introduce a system for automated AK detection in CFC areas.For the differentiation of AK from healthy skin areas and co-localized benign growths (Seborrheic Keratosis/Lentigo Solaris; SK/LS), cross-polarized digital photographs of afflicted skin surfaces were taken, and a convolutional neural network (AKCNN) whose convolution part was optimally transferred from a pre-trained VGG16 was implemented. For the detection of multifocal AK in wide skin regions, superpixels were employed to generate region patches for the subsequent evaluation. AKCNN was implemented and evaluated in 19739, 43067, and 12,205 image patches of AK, SK/LS, and healthy skin, respectively, originating from 46 patients. AKCNN performance was assessed in two ways: (a) patch classification using the macro averaged F1 score and (b) AK burden evaluation in broad skin areas using an adapted region-based F1 (aF1) score.Using raw clinical images, AKCNN exhibited a macro F1 of 0.78 at patch level and a region-based aF1 of 0.81, with good tolerance against image scaling.The proposed system efficiently uses cross-polarized clinical photography to assess the AK burden within the CFC.

Defect of IL17 Signaling, but Not Centrinone, Inhibits the Development of Psoriasis and Skin Papilloma in Mouse Models.

Patients with psoriasis tend to develop skin cancer, and the hyperproliferation of the epidermis is a histopathological hallmark of both psoriasis and cutaneous squamous cell carcinoma (SCC), indicating that they may share pathogenic mechanisms. Interleukin-17 (IL17) stimulates the proliferation of the epidermis, leading to psoriasis. Overexpression of Polo-like kinase 4 (PLK4), which controls centriole duplication, has been identified in SCC, which also shows the hyperproliferation of keratinocytes. To investigate the cooperation between IL17 signaling and centriole duplication in epidermal proliferation, we established psoriasis and skin papilloma models in wild type (WT), IL17 receptor A (T779A) knockin (Il17ra(T779A)-KI), and IL17 receptor C knockout (Il17rc-KO) mouse strains. Bioinformatics, Western blot, immunohistochemical staining, colony formation, and real-time PCR were used to determine the effect of IL17 signaling and centrinone on epithelial proliferation. In the psoriasis model, compared to WT and Il17ra(T779A)-KI, Il17rc-KO dramatically suppressed epidermal thickening. The proliferation of keratinocytes significantly decreased in this order from WT to Il17ra(T779A)-KI and Il17rc-KO mice. In the skin papilloma model, Il17ra(T779A)-KI significantly decreased tumor burden compared to the WT, while Il17rc-KO abolished papilloma development. However, centrinone, a selective inhibitor of PLK4, did not affect skin lesion formation in either model. Our data demonstrated that Il17ra(T779A)-KI and Il17rc-KO prevent the development of psoriasis and tumorigenesis in the skin, while the topical administration of centrinone does not have any effect.

Allergen Composition, Marketing Claims, and Affordability of Pediatric Sunscreens.

Childhood sun exposure is associated with development of future skin cancers. Sunscreens are an important tool to prevent harmful ultraviolet rays. The aims of the study are to evaluate sunscreens targeted to children and to analyze cost, marketing claims, ingredients, and allergens to help consumers select products. The top 50 pediatric sunscreens across retailers were analyzed for their cost, marketing claims, ingredients, vehicles, and containers. Ingredients were compared with the American Contact Dermatology Society 2020 Core Allergen List. The mean price was $6.20 per ounce (range, $0.25-$39.98). The mean sun protection factor was 48.5 (range, 30-100; SD, 48.5). There was a mean of 17.5 ingredients and a mean of 1.1 allergens in products. On average, products marketed as "sensitive skin" were not only significantly more expensive ($8.90 vs $3.50 per ounce, P = 0.01) but also were significantly more likely to not contain any allergens (36.0%, n = 18 vs 12%, n = 6; P = 0.05). Products with mineral-only UV blockers were significantly less likely to have any allergen when compared with products that had chemical UV blockers (5.6%, n = 1 vs 94.4%, n = 17; P = 0.02). The current market of pediatric sunscreens varies significantly in price, marketing claims, and active ingredients. Products marked as suitable for sensitive skin had significantly fewer allergens, but a majority of these products still had at least one allergen. Many sunscreens contain contact allergens, which is an important selection consideration.

LIPOPOLYSACCHARIDE INHIBITS AUTOPHAGY IN HUMAN DERMAL FIBROBLASTS IN VITRO

Objective: Fibroblasts are mesenchymal cells of dermal origin that provide structural integrity for connective tissue by producing the extracellular matrix proteins. They are the dominant component of the tumor microenvironment and are then referred to as cancer-associated fibroblasts (CAFs). CAFs play an important role in cancer cell growth. Autophagy is an intracellular self-degradative process that balances cell energy sources and regulates tissue homeostasis. Autophagy is now considered a critical process in skin health and skin cancer. The objective of this study is to investigate the effect of lipopolysaccharide (LPS) on the autophagy mechanism in human dermal fibroblasts (HDFs) in vitro. Methods: HDFs were incubated with 0.1, 0.5, 1 and 5 μg/mL of LPS for 24 h. The viability of cells was determined using WST-1 assay. The protein expressions of beclin-1, p62, LC3-I and LC3-II were analyzed by Western blotting. Results: The viability of HDFs incubated with 0.1, 0.5, 1 and 5 μg/mL of LPS did not show any significant differences compared to untreated cells. Beclin-1 protein expression was upregulated with all LPS concentrations. The protein expression of p62 was also induced with all LPS concentrations. Furthermore, the ratio of LC3-II/LC3-I protein expression was increased with all LPS concentrations. Conclusion: Our results demonstrate that LPS inhibits autophagy in HDFs through the upregulation of p62 and LC3 protein expression. These findings suggest the relationship between inflammation and autophagy in skin cells and might contribute to understanding the key role of autophagy in the development of skin cancer.

Is there a Link between Non Melanoma Skin Cancer and Hydrochlorothiazide?

Here in we evaluated the association between the use of Hydrochlorothiazide (HCTZ) and the risk of NMSC both, basal cell carcinoma (BCC) and squamous cell carcinoma (SCC). Even though the use of HCTZ is not linked with the development of serious adverse drug reactions, non-melanoma skin cancer (NMSC) has been reported in patients treated with the drug in recent years, most likely due to its photosensitizing ability. To evaluate the statistically significant difference (P<0.05) in the development of NMSC between HCTZ users and non-users and the correlation (P<0.05) between HCTZ use and NMSC. We performed a retrospective study on patients referred to general practitioners who developed skin cancer or NMSC whether or not they were treated with antihypertensive drugs. Controls were matched with the test by age and sex. We calculated odds ratios (ORs) for skin cancer and NMSC associated with hydrochlorothiazide using conditional logistic regression. We enrolled 19,320 patients in the present study, out of a total of 10,110 (52.3%) who were treated with antihypertensive drugs. Of 10,110 patients, 3,870 were treated with HCTZ (38.3%). During the study, we failed to report an increased risk of NMSC in HCTZ-treated vs. untreated patients. Gender stratification revealed an OR for NMSC of 1.36 for men and 0.56 for women. We did not find a dose-response relationship between HCTZ use and NMSC. In the present study, we failed to report an association between the use of HCTZ and the development of NMSC.

Lymphocyte subsets and Langerhans cells in the skin of kidney transplant recipients under three different immunosuppressive regimens.

Renal transplant recipients (RTRs) are at increased risk of developing skin cancer; however, the role of immunosuppression is not yet fully understood. In this study, we evaluated the immunohistochemical changes in the skin of RTRs under three different immunosuppression regimens: mTOR inhibitors (mTORi), sirolimus or everolimus, mycophenolic acid (MPA) precursors such as mycophenolate sodium or mofetil, or azathioprine (AZA). We evaluated biopsies of sun-exposed and sun-protected skin for immunohistochemical quantification of B lymphocytes (CD20+ ), T lymphocytes (CD3+ , CD4+ , and CD8+ ), and Langerhans cells (LCs) (CD1a+ ) in 30 RTRs and 10 healthy controls. The RTRs were divided into three groups: mTORi (n = 10), MPA (n = 10), and AZA (n = 10). No differences were observed in the number of B lymphocytes. However, a significant decrease in the number of T lymphocytes and LCs was observed in both sun-protected and sun-exposed skin in the AZA and MPA groups, although to a lesser degree in the latter group. The skin of the mTORi group did not differ from that of the control group in terms of the number of B and T lymphocytes and LCs. Patients treated with mTORi exhibit preserved cellular elements related to cutaneous immune surveillance. The use of AZA induced a greater degree of skin immunosuppression than in the control group, as demonstrated by the decrease in T lymphocytes and LCs.

104 Loss of Kdm6a and Trp53 drives the development of squamous cell skin cancer in mice

Cutaneous squamous cell carcinoma (cSCC) has among the highest mutation burdens of all cancers, reflecting its association with the mutagenic effects of ultraviolet light. Though mutations in established, cancer-relevant genes like TP53 and NOTCH1 are prevalent in cSCC, they are tolerated in clinically normal skin and are insufficient to cause skin cancer. Whether epigenetic regulators cooperate in the development of squamous cell carcinoma is just starting to be defined. KDM6A encodes a histone H3K27me2/me3 demethylase that is frequently mutated in cSCC and other cancers.

581 Topical calcipotriol plus imiquimod immunotherapy for non-keratinocyte skin cancers

Non-keratinocyte cutaneous malignancies including breast cancer cutaneous metastasis and melanoma in situ are often poor surgical candidates due to their anatomical location, size and the morbidities associated with surgery. Imiquimod, a toll-like receptor 7 agonist, is used for the treatment of these cutaneous malignancies, which activates the innate immunity in the skin. However, imiquimod’s modest effect on the activation of adaptive immunity limits its efficacy as a monotherapy. We have previously demonstrated that topical induction of thymic stromal lymphopoietin (TSLP) cytokine by calcipotriol protects against skin and breast cancer development by directly activating T cell immunity.

608 Development and assessment of nanoparticle-encapsulated sunscreens

The risk of developing skin cancer from ultraviolet radiation (UVR) can be mitigated with sunscreens. Safety and aesthetic concerns about commercial sunscreens have led to our development of a bioadhesive nanoparticle (BNP) sunscreen platform. Building upon prior work encapsulating FDA-approved agents avobenzone and octocrylene, we have now also encapsulated EU-approved agents diethylamino hydroxybenzoyl hexyl benzoate (DHHB) and octinoxate (OCX) with 50% and 30% loading, respectively. Nonadhesive nanoparticles (NNPs) are produced initially and can be converted to BNPs, which possess an aldehyde-rich corona that can bind epidermal amines.