scholarly journals Extended UVB Exposures Alter Tumorigenesis and Treatment Efficacy in a Murine Model of Cutaneous Squamous Cell Carcinoma

2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Erin M. Burns ◽  
Kathleen L. Tober ◽  
Judith A. Riggenbach ◽  
Donna F. Kusewitt ◽  
Gregory S. Young ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Malignant Tumors ◽  
Tumor Development ◽  
Sun Exposure ◽  
Epidemiological Studies ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Exposure Model ◽  
Uvb Exposure

Epidemiological studies support a link between cumulative sun exposure and cutaneous squamous cell carcinoma (SCC) development. However, the presumed effects of extended ultraviolet light B (UVB) exposure on tumorigenesis in the sexes have not been formally investigated. We examined differences in ultimate tumorigenesis at 25 weeks in mice exposed to UVB for either 10 or 25 weeks. Additionally, we investigated the effect of continued UVB exposure on the efficacy of topical treatment with anti-inflammatory (diclofenac) or antioxidant (C E Ferulic or vitamin E) compounds on modulating tumorigenesis. Vehicle-treated mice in the 25-week UVB exposure model exhibited an increased tumor burden and a higher percentage of malignant tumors compared to mice in the 10-week exposure model, which correlated with increases in total and mutant p53-positive epidermal cells. Only topical diclofenac decreased tumor number and burden in both sexes regardless of UVB exposure length. These data support the commonly assumed but not previously demonstrated fact that increased cumulative UVB exposure increases the risk of UVB-induced SCC development and can also affect therapeutic efficacies. Our study suggests that cessation of UVB exposure by at-risk patients may decrease tumor development and that topical NSAIDs such as diclofenac may be chemopreventive.

scholarly journals Targeting 14-3-3ε activates apoptotic signaling to prevent cutaneous squamous cell carcinoma

2020 ◽  
Author(s):  
Thomas R Holmes ◽  
Jenan Al Matouq ◽  
Matti Holmes ◽  
Natasha Sioda ◽  
Justin C Rudd ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Death ◽  
Skin Cancer ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Tumor Development ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Malignant Progression ◽  
Skin Tumor ◽  
Premalignant Lesions

Abstract More than a million cases of cutaneous squamous cell carcinoma are diagnosed in the USA each year, and its incidence is increasing. Most of these malignancies arise from premalignant lesions, providing an opportunity for intervention before malignant progression. We previously documented how cytoplasmic mislocalization of CDC25A in premalignant and malignant skin cancers confers resistance to apoptotic cell death via a mechanism that depends on its interaction with 14-3-3ε. From these data, we hypothesized that 14-3-3ε overexpression drives skin tumor development and progression, such that targeting 14-3-3ε may be a useful strategy for skin cancer treatment. Like CDC25A, 14-3-3ε was overexpressed and mislocalized to the cytoplasm of both benign and malignant human skin cancer. Skin-targeted deletion of the 14-3-3ε gene reduced skin tumor development by 75% and blocked malignant progression. 14-3-3ε suppressed apoptosis through activation of Akt, leading to inhibition of BCL2 associated agonist of cell death and upregulation of Survivin. Using virtual tetrapeptide libraries, we developed a novel peptide that specifically blocked 14-3-3ε heterodimerization and thereby prevented its interaction with CDC25A. The peptide reduced prosurvival signaling, killed skin cancer cells and reduced skin tumor growth in xenograft. Normal skin keratinocytes were unaffected by inhibition or deletion of 14-3-3ε. Thus, targeting of 14-3-3ε dimerization is a promising strategy for the treatment of premalignant skin lesions.

scholarly journals Genetic ancestry, skin pigmentation, and the risk of cutaneous squamous cell carcinoma in Hispanic/Latino and non-Hispanic white populations

2020 ◽  
Vol 3 (1) ◽  
Author(s):  
Eric Jorgenson ◽  
Hélène Choquet ◽  
Jie Yin ◽  
Thomas J. Hoffmann ◽  
Yambazi Banda ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Skin Pigmentation ◽  
Sun Exposure ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Genetic Ancestry ◽  
European Ancestry ◽  
History Of ◽  
Hispanic Latinos

AbstractAlthough cutaneous squamous cell carcinoma (cSCC) is one of the most common malignancies in individuals of European ancestry, the incidence of cSCC in Hispanic/Latinos is also increasing. cSCC has both a genetic and environmental etiology. Here, we examine the role of genetic ancestry, skin pigmentation, and sun exposure in Hispanic/Latinos and non-Hispanic whites on cSCC risk. We observe an increased cSCC risk with greater European ancestry (P = 1.27 × 10−42) within Hispanic/Latinos and with greater northern (P = 2.38 × 10−65) and western (P = 2.28 × 10−49) European ancestry within non-Hispanic whites. These associations are significantly, but not completely, attenuated after considering skin pigmentation-associated loci, history of actinic keratosis, and sun-protected versus sun-exposed anatomical sites. We also report an association of the well-known pigment variant Ala111Thr (rs1426654) at SLC24A5 with cSCC in Hispanic/Latinos. These findings demonstrate a strong correlation of northwestern European genetic ancestry with cSCC risk in both Hispanic/Latinos and non-Hispanic whites, largely but not entirely mediated through its impact on skin pigmentation.

scholarly journals Oh, the Mutations You’ll Acquire! A Systematic Overview of Cutaneous Squamous Cell Carcinoma

2021 ◽  
Vol 55 (S2) ◽  
pp. 89-119
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Sun Exposure ◽  
The United States ◽  
Cutaneous Squamous Cell Carcinoma ◽  
Targeted Therapeutics ◽  
Invasion And Metastasis ◽  
Mutational Burden ◽  
Significant Mortality

Nearly two million cases of cutaneous squamous cell carcinoma (cSCC) are diagnosed every year in the United States alone. cSCC is notable for both its prevalence and its propensity for invasion and metastasis. For many patients, surgery is curative. However, patients experiencing immunosuppression or recurrent, advanced, and metastatic disease still face limited therapeutic options and significant mortality. cSCC forms after decades of sun exposure and possesses the highest known mutation rate of all cancers. This mutational burden complicates efforts to identify the primary factors driving cSCC initiation and progression, which in turn hinders the development of targeted therapeutics. In this review, we summarize the mutations and alterations that have been observed in patients’ cSCC tumors, affecting signaling pathways, transcriptional regulators, and the microenvironment. We also highlight novel therapeutic opportunities in development and clinical trials.

scholarly journals Chronic sun exposure-related fusion oncogenes EGFR-PPARGC1A in cutaneous squamous cell carcinoma

2017 ◽  
Vol 7 (1) ◽  
Author(s):  
Sho Egashira ◽  
Masatoshi Jinnin ◽  
Manami Ajino ◽  
Naoki Shimozono ◽  
Sayo Okamoto ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Sun Exposure ◽  
Cutaneous Squamous Cell Carcinoma

Expression of FOXE1 in Cutaneous Squamous Cell Carcinoma

2019 ◽  
Vol 6 (1) ◽  
pp. 1-4
Author(s):  
Meng Liu ◽  
Yan Zheng ◽  
Mengdi Zhang ◽  
Qiqi Duan ◽  
Shengxiang Xiao
Keyword(s):  
Squamous Cell Carcinoma ◽  
Tumor Suppressor ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Malignant Tumors ◽  
Cutaneous Squamous Cell Carcinoma ◽  
The Common ◽  
Melanoma Skin

Cutaneous squamous cell carcinoma (cSCC) is one of the common non-melanoma skin malignant tumors with sophisticated pathogenesis. FOXE1 is considered to be a tumor suppressor involved in the development of various tumors; however, the expression and significance of FOXE1 in cSCC remains to be investigated.

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