Cutaneous Squamous Cell Carcinoma

Waldman, Abigail; Schmults, Chrysalyne D.

doi:10.1016/j.hoc.2018.08.001

Cited by 281 publications

(216 citation statements)

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“…Indeed, during the K562-based preliminary screening, they were interesting candidates for a multifunctional approach, exhibiting, in addition to anti-oxidant activity, cell growth inhibitory and pro-apoptotic activity. This has the potential to have a significant impact, also when considering the known skin tumorigenesis inhibition of hesperidin [44], which drives attention towards this, and related compounds, as a possible preventive agent in the treatment of some human pathologies, such as UV induced neoplastic diseases [45], squamous cell carcinoma (SCC) [46], malignant melanomas [47], non-melanoma skin tumors [48], and psoriasis-associated skin cancers [49]. In this context, hesperidin derivatives should be tested on the several "in vitro" experimental model systems available for these pathologies [50,51], as well as on "in vivo" mouse models for skin cancers [52,53].…”

Section: Discussionmentioning

confidence: 99%

Novel Lipidized Derivatives of the Bioflavonoid Hesperidin: Dermatological, Cosmetic and Chemopreventive Applications

et al. 2018

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Hesperidin is one of the most important natural flavonoids, known for its antioxidant, anti-inflammatory, anti-mutagenic, and anti-hypertensive properties. Despite its various biological activities, hesperidin is rarely used in the dermo-cosmetic field because of its poor solubility in both water and oil phases that makes difficult formulation, distribution and bioavailability through the skin layers. Moreover, hesperidin is still underestimated in skin care products, and literature data on its stability into a topical formulation are not yet available. In this paper we report the synthesis of five different derivatives of hesperidin and their evaluation in terms of antioxidant, antifungal, antiproliferative, and apoptotic effects on human leukemic K562 cells. Preliminary antiproliferative effects were considered since hyper-proliferation is involved in several cutaneous problems particularly in the case of photo-exposition and environmental pollution. Esp4 and Esp5 were found to be more active in inhibiting K562 cell growth than parent hesperidin. Esp3 exhibited different biological properties, i.e., antioxidant activity in the absence of antiproliferative effects.

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Section: Discussionmentioning

confidence: 99%

Novel Lipidized Derivatives of the Bioflavonoid Hesperidin: Dermatological, Cosmetic and Chemopreventive Applications

et al. 2018

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“…Cutaneous squamous cell carcinoma (cSCC) most commonly arises in actinically damaged skin and accounts for 25% of cutaneous malignancies diagnosed in the Caucasian population [1]. The incidence of cSCC continues to rise annually, with an estimated 50-200% increase in incidence in the last three decades in USA alone, and is predicted to increase in future years due to an aging global population [2]. Solar ultraviolet radiation is the primary environmental extrinsic cause of cSCC.…”

Section: Introductionmentioning

confidence: 99%

“…However, cSCC can demonstrate dramatic histopathological heterogeneity, resulting in a wide range of clinical outcomes [7]. Histopathologic subtypes of cSCC are broadly divided into low-grade SCC (Figure 1A) that are well-differentiated but have low metastatic potential (keratoacanthomas, SCC in situ and verrucous carcinoma), or high-grade SCC (Figure 1B) that are poorly differentiated, have high potential of metastasis and recurrence, and are associated with a poor prognosis for patients (desmoplastic cSCC, adenosquamous cSCC and cSCC associated with non-healing ulcers or scarring processes arising from chronic wounds) [2,7]. Once developed, the natural history of untreated SCC is one of local invasion followed by metastasis via the lymphatic system, blood or perineural invasion, which can lead to death [7].…”

mentioning

confidence: 99%

“…These parameters are used in clinical staging systems for cSCC [3]. Management of cSCC is primarily surgical, with adjuvant chemoradiation approaches based on risk factors, patient and tumor features, as well as care features including access to treatment and associated costs [2].With increasingly longer life expectancy, the health and economic burden of cSCC is likely to continue to increase significantly. Hence, a better understanding of factors contributing to cSCC progression and metastasis is necessary to aid development of novel therapies, aimed at combatting cSCC in the community.…”

mentioning

confidence: 99%

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confidence: 99%

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Mechanical Force and Actin Dynamics during Cutaneous Squamous Cell Carcinoma (cSCC) Progression: Opportunities for Novel Treatment Modalities

Boyle¹,

Kopecki²

2020

Squamous Cell Carcinoma - Hallmark and Treatment Modalities

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Cutaneous squamous cell carcinoma (cSCC) accounts for 25% of cutaneous malignancies diagnosed in the Caucasian population. Surgical removal in combination with radio-and chemotherapy is an effective treatment; however, prognosis for patients suffering from aggressive cSCC is still relatively poor. Increasing prevalence coupled with high mortality and morbidity in aggressive metastatic forms of cSCC highlights the need for development of novel targeted therapeutics. Metastasis is a complex process requiring dramatic reorganization of the cell cytoskeleton. Recent studies have highlighted the importance of mechanical forces and actin dynamics in cancer cells' intrinsic ability to invade adjacent tissues, intravasate into vasculature, and ultimately metastasize. Tight regulation of the biochemical and mechanical properties of the actin cytoskeleton drives cellular processes involved in cSCC progression including polarity establishment, morphogenesis, and motility. Here we will provide a short introduction to disease pathogenesis, give an overview of the role of key regulatory proteins governing the mechanical forces and actin dynamics critical to cSCC progression, and describe the contribution of actin remodeling and actomyosin signaling to cSCC progression. We will also discuss how targeting protein regulating mechanical force and actin dynamics may have clinical utility in development of novel treatment modalities for patients suffering from aggressive cSCC.Squamous Cell Carcinoma -Hallmark and Treatment Modalities 2 immunosuppression, the second most common cause, leads to the formation of aggressive cSCC in organ transplant patients, patients on immunomodulatory therapies, and those suffering from recessive dystrophic epidermolysis bullosa, a genetic skin blistering disease [3][4][5]. The incidence of cSCC is higher in individuals who are fair-skinned and have a sun-sensitive phenotype; however, the aggressive forms of cSCC are more common in men and the elderly [3]. Despite its prevalence, the relatively low fatality rate of cSCC means that its health and economic burden is often substantially underestimated [3], albeit latest data showing that in addition to significant morbidity cSCC accounts for up to 8000 deaths per year and costs approximately $4.8 billion annually in USA alone [6].cSCC generally presents as a scaly, red or bleeding abnormal lesion on sunexposed areas, and is associated with relatively benign outcomes and a low risk of metastasis. However, cSCC can demonstrate dramatic histopathological heterogeneity, resulting in a wide range of clinical outcomes [7]. Histopathologic subtypes of cSCC are broadly divided into low-grade SCC (Figure 1A) that are well-differentiated but have low metastatic potential (keratoacanthomas, SCC in situ and verrucous carcinoma), or high-grade SCC (Figure 1B) that are poorly differentiated, have high potential of metastasis and recurrence, and are associated with a poor prognosis for patients (desmoplastic cSCC, adenosquamous cSCC and cSCC associated with non-healing...

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Association of Vitamin A Intake With Cutaneous Squamous Cell Carcinoma Risk in the United States

Kim

Park

et al. 2019

JAMA Dermatol

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IMPORTANCE Retinoids are bioactive forms of vitamin A that are essential in the maintenance of epithelial maturation and differentiation. Synthetic retinoids are used in chemoprevention of skin cancer among high-risk populations with potential adverse effects. Epidemiologic data on vitamin A intake and risk of cutaneous squamous cell carcinoma (SCC) are limited. OBJECTIVE To examine whether vitamin A intake is associated with a reduction in SCC risk. DESIGN, SETTINGS, AND PARTICIPANTS This cohort study prospectively examined intake of vitamin A and carotenoids and SCC risk in the Nurses' Health Study (1984-2012) and the Health Professionals Follow-up Study (1986-2012). Diet was assessed repeatedly. Incident SCC was confirmed by pathologic reports. Data analysis was performed from June 21, 2017, to December 4, 2018. EXPOSURES Intakes of vitamin A, retinol, and carotenoids. MAIN OUTCOMES AND MEASURES Incident SCC. Cox proportional hazards regression models were used to compute cohort-specific hazard ratios (HRs) and 95% CIs. Pooled HRs of the cohort-specific results were calculated. RESULTS A total of 3978 SCC cases in 75 170 women in the Nurses' Health Study (mean [SD] age, 50.4 [7.2] years) and 48 400 men in the Health Professionals Follow-up Study (mean [SD] age, 54.3 [9.9] years) were documented. Higher total vitamin A was associated with a reduction in SCC risk; with quintile 1 as the reference, the pooled multivariate HRs for the increasing quintiles of vitamin A intake were 0.97 (95% CI, 0.87-1.07) for quintile 2, 0.97 (95% CI, 0.80-1.17) for quintile 3, 0.93 (95% CI, 0.84-1.03) for quintile 4, and 0.83 (95% CI, 0.75-0.93) for quintile 5 (P < .001 for trend). Higher intakes of retinol and some carotenoids were also associated with a reduction in SCC risk; the pooled HRs for the highest quintiles of intake compared with the lowest quintiles were 0.88 (95% CI, 0.79-0.97; P = .001 for trend) for total retinol, 0.86 (95% CI, 0.76-0.96; P = .001 for trend) for beta cryptoxanthin, 0.87 (95% CI, 0.78-0.96; P < .001 for trend) for lycopene, and 0.89 (95% CI, 0.81-0.99; P = .02 for trend) for lutein and zeaxanthin. The results were generally consistent by sex and other SCC risk factors. CONCLUSIONS AND RELEVANCE This study suggests that increased intake of dietary vitamin A is associated with decreased risk of incident SCC. Future studies are needed to determine whether vitamin A supplementation has a role in chemoprevention of SCC.

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Cutaneous Squamous Cell Carcinoma

Cited by 281 publications

References 74 publications

Novel Lipidized Derivatives of the Bioflavonoid Hesperidin: Dermatological, Cosmetic and Chemopreventive Applications

Novel Lipidized Derivatives of the Bioflavonoid Hesperidin: Dermatological, Cosmetic and Chemopreventive Applications

Mechanical Force and Actin Dynamics during Cutaneous Squamous Cell Carcinoma (cSCC) Progression: Opportunities for Novel Treatment Modalities

Association of Vitamin A Intake With Cutaneous Squamous Cell Carcinoma Risk in the United States

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