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Bioengineered Dec 2021The aim of this study is to explore the role of mammalian target of rapamycin (mTOR) in cutaneous squamous cell carcinoma (CSCC), Bowen's disease (BD), and actinic...
The aim of this study is to explore the role of mammalian target of rapamycin (mTOR) in cutaneous squamous cell carcinoma (CSCC), Bowen's disease (BD), and actinic keratosis (AK) with squamous cell differentiation abnormality and its relationship with the degree of tumor proliferation. Thirty cases of clinical paraffin specimens of CSCC, BD, and AK were each collected from Jinhua Fifth Hospital, while 30 cases of normal skin specimens surgically resected in Department of Plastic Surgery were selected as controls. The expressions of mTOR and Ki-67 in tissues were detected by immunohistochemical staining. The positive expression rate of mTOR in the CSCC group was higher than those in the BD group and AK group ( < 0.05), while it was higher in the BD group and AK group than in the normal skin group ( < 0.05). The CSCC group had a higher positive expression rate of Ki-67 than the AK group ( < 0.01). The results of logistic regression analysis showed that the pathogenic site [odds ratio (OR) = 1.189, 95% confidence interval (95%CI): 1.028-1.381, = 0.021], course of disease (OR = 2.059, 95%CI: 1.036-4.087, = 0.043), and differentiation degree (OR = 1.325, 95%CI: 1.169-1.512, = 0.001) were independent factors for the positive expression of mTOR. OR>1, indicating that the factor is a risk factor. The expression levels of mTOR in CSCC, BD, and AK were positively correlated with the expression level of Ki-67 ( = 0.827, < 0.01, = 0.608, < 0.01, = 0.368, = 0.045). These results suggest that mTOR may be involved in the pathogenesis of CSCC, and related to the proliferation degree of CSCC, as an index reflecting the proliferation status of CSCC.
Topics: Adult; Aged; Aged, 80 and over; Bowen's Disease; Carcinoma, Squamous Cell; Female; Humans; Keratosis, Actinic; Ki-67 Antigen; Logistic Models; Male; Middle Aged; Precancerous Conditions; Skin; Skin Neoplasms; TOR Serine-Threonine Kinases
PubMed: 34874800
DOI: 10.1080/21655979.2021.1984719 -
Journal of the American Academy of... Mar 2021Population-based studies analyzing hydrochlorothiazide's (HCTZ's) effect on keratinocyte carcinoma, and particularly invasive squamous cell carcinoma (SCC), are lacking.
BACKGROUND
Population-based studies analyzing hydrochlorothiazide's (HCTZ's) effect on keratinocyte carcinoma, and particularly invasive squamous cell carcinoma (SCC), are lacking.
OBJECTIVES
To characterize the association between HCTZ use and invasive SCC, SCC in situ (SCCis), and basal cell carcinoma (BCC).
METHODS
This population-based case-control study included all 6880 patients diagnosed with first-time BCC, SCCis, and invasive SCC between 2003 and 2017 in Iceland and 69,620 population controls. Conditional logistic regression analyses were used to calculate multivariate odds ratios (ORs) for keratinocyte carcinoma associated with HCTZ use.
RESULTS
A cumulative HCTZ dose above 37,500 mg was associated with increased risk of invasive SCC (OR, 1.69; 95% confidence interval [CI], 1.04-2.74). Users of HCTZ also had an increased risk of SCCis (OR, 1.24; 95% CI, 1.01-1.52) and BCC (OR, 1.14; 95% CI, 1.02-1.29).
LIMITATIONS
Limitations include this study's retrospective nature with the resulting inability to adjust for ultraviolet exposure, Fitzpatrick skin type, and comorbidities.
CONCLUSIONS
High cumulative exposure to HCTZ is associated with the development of keratinocyte carcinoma and, most importantly, invasive SCC. Sun protective behaviors alone may not eliminate the carcinogenic potential of HCTZ.
Topics: Aged; Aged, 80 and over; Antihypertensive Agents; Carcinogenesis; Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Case-Control Studies; Female; Humans; Hydrochlorothiazide; Hypertension; Iceland; Male; Middle Aged; Risk Factors; Skin; Skin Neoplasms; Time Factors
PubMed: 32791082
DOI: 10.1016/j.jaad.2020.08.025 -
Laryngo- Rhino- Otologie Feb 2024
Topics: Humans; Carcinoma, Squamous Cell; Skin Neoplasms; Skin
PubMed: 38320566
DOI: 10.1055/a-2211-409 -
Science Advances Jan 2021In ultraviolet (UV) radiation-exposed skin, mutations fuel clonal cell growth. The relationship between UV exposure and the accumulation of clonal mutations (CMs) and...
In ultraviolet (UV) radiation-exposed skin, mutations fuel clonal cell growth. The relationship between UV exposure and the accumulation of clonal mutations (CMs) and the correlation between CMs and skin cancer risk are largely unexplored. We characterized 450 individual-matched sun-exposed (SE) and non-SE (NE) normal human skin samples. The number and relative contribution of CMs were significantly different between SE and NE areas. Furthermore, we identified hotspots in , , and where mutations were significantly associated with UV exposure. In the normal skin from patients with cutaneous squamous cell carcinoma, we found that the cancer burden was associated with the UV-induced mutations, with the difference mostly conferred by the low-frequency CMs. These findings provide previously unknown information on UV's carcinogenic effect and pave the road for future development of quantitative assessment of subclinical UV damage and skin cancer risk.
Topics: Carcinoma, Squamous Cell; Humans; Mutation; Skin; Skin Neoplasms; Ultraviolet Rays
PubMed: 33523857
DOI: 10.1126/sciadv.abd7703 -
Environmental Pollution (Barking, Essex... May 2020Environmental exposure to arsenic is a major public health challenge worldwide. In detailing the hallmark signs of chronic arsenic exposure, previous studies have shown...
Environmental exposure to arsenic is a major public health challenge worldwide. In detailing the hallmark signs of chronic arsenic exposure, previous studies have shown that epigenetic and immune dysfunction are associated with arsenic-induced skin lesions; however, knowledge regarding interactions between the mechanisms listed above is limited. In this study, a total of 106 skin samples were collected over the past 20 years. Based on the presence or absence of high arsenic exposure, the participants were divided into arsenic exposure (72) and reference (34) groups. Additionally, the arsenic exposure group was further divided into the non-cancer group (31, including skin hyperpigmentation and hyperkeratosis) and the skin cancer group (41, including Bowen's disease, basal cell carcinoma and squamous cell carcinoma) according to a skin histopathological examination. First, the associations among miR-155, NF-AT1 with immunological dysfunction and arsenic-induced skin lesions and carcinogenesis were confirmed using these skin samples. In the arsenic-exposed group, miR-155-5p, keratin 1(Krt1), keratin 10 (Krt10), and keratin 6c (Krt6c) were significantly increased in the skin (p < 0.05), while NF-AT1, interleukin-2 (IL-2), and interferon-γ (IFN-γ) were significantly decreased (p < 0.05). Clear correlations were observed among these factors (p < 0.05). In immortalized human keratinocytes, silencing and overexpression of NF-AT1 could alter the expression and secretion of immunological dysfunction indicators (IL-2 and IFN-γ) that are induced by arsenic exposure (p < 0.05); however, miR-155-5p levels did not change significantly (p > 0.05). The miR-155-5p mimic and inhibitor could regulate the NF-AT1-mediated immunological dysfunction caused by arsenic (p < 0.05). Our study provides some limited evidence that miR-155-5p regulates the NF-AT1-mediated immunological dysfunction that is involved in the pathogenesis and carcinogenesis of arsenic. The second major finding was that Krt1 and Krt10 are markers of hyperkeratosis caused by arsenic, and Krt6c is a potential biomarker that can reflect arsenic carcinogenesis.
Topics: Arsenic; Carcinoma, Squamous Cell; Environmental Pollutants; Humans; Skin; Skin Neoplasms
PubMed: 31995775
DOI: 10.1016/j.envpol.2020.113919 -
Journal of Experimental & Clinical... Jul 2023Cutaneous squamous cell carcinoma (cSCC) is the second most prevalent form of skin cancer, showing a rapid increasing incidence worldwide. Although most cSCC can be...
BACKGROUND
Cutaneous squamous cell carcinoma (cSCC) is the second most prevalent form of skin cancer, showing a rapid increasing incidence worldwide. Although most cSCC can be cured by surgery, a sizeable number of cases are diagnosed at advanced stages, with local invasion and distant metastatic lesions. In the skin, neurotrophins (NTs) and their receptors (CD271 and Trk) form a complex network regulating epidermal homeostasis. Recently, several works suggested a significant implication of NT receptors in cancer. However, CD271 functions in epithelial tumors are controversial and its precise role in cSCC is still to be defined.
METHODS
Spheroids from cSCC patients with low-risk (In situ or Well-Differentiated cSCC) or high-risk tumors (Moderately/Poorly Differentiated cSCC), were established to explore histological features, proliferation, invasion abilities, and molecular pathways modulated in response to CD271 overexpression or activation in vitro. The effect of CD271 activities on the response to therapeutics was also investigated. The impact on the metastatic process and inflammation was explored in vivo and in vitro, by using zebrafish xenograft and 2D/3D models.
RESULTS
Our data proved that CD271 is upregulated in Well-Differentiated tumors as compared to the more aggressive Moderately/Poorly Differentiated cSCC, both in vivo and in vitro. We demonstrated that CD271 activities reduce proliferation and malignancy marker expression in patient-derived cSCC spheroids at each tumor grade, by increasing neoplastic cell differentiation. CD271 overexpression significantly increases cSCC spheroid mass density, while it reduces their weight and diameter, and promotes a major fold-enrichment in differentiation and keratinization genes. Moreover, both CD271 overexpression and activation decrease cSCC cell invasiveness in vitro. A significant inhibition of the metastatic process by CD271 was observed in a newly established zebrafish cSCC model. We found that the recruitment of leucocytes by CD271-overexpressing cells directly correlates with tumor killing and this finding was further highlighted by monocyte infiltration in a THP-1-SCC13 3D model. Finally, CD271 activity synergizes with Trk receptor inhibition, by reducing spheroid viability, and significantly improves the outcome of photodynamic therapy (PTD) or chemotherapy in spheroids and zebrafish.
CONCLUSION
Our study provides evidence that CD271 could prevent the switch between low to high-risk cSCC tumors. Because CD271 contributes to maintaining active differentiative paths and favors the response to therapies, it might be a promising target for future pharmaceutical development.
Topics: Animals; Humans; Carcinoma, Squamous Cell; Skin Neoplasms; Zebrafish; Cell Line, Tumor; Epidermis; Cell Proliferation; Gene Expression Regulation, Neoplastic
PubMed: 37443031
DOI: 10.1186/s13046-023-02737-7 -
Cutis Sep 2023Endocrine mucin-producing sweat gland carcinoma (EMPSGC) and primary cutaneous mucinous carcinoma (PCMC) are rare low-grade neoplasms thought to arise from apocrine...
Endocrine mucin-producing sweat gland carcinoma (EMPSGC) and primary cutaneous mucinous carcinoma (PCMC) are rare low-grade neoplasms thought to arise from apocrine glands that share many histological features and are proposed to be on a single histopathologic continuum, with EMPSGC as the in situ form that may progress to the invasive PCMC. Management involves a metastatic workup and either wide local excision (WLE) with greater than 5 mm margins or Mohs micrographic surgery (MMS) in anatomically sensitive areas. We present 2 cases of EMPSGC and 3 cases of PCMC and review their clinical and histopathologic features, differential diagnoses, and treatment.
Topics: Humans; Adenocarcinoma, Mucinous; Sweat Gland Neoplasms; Carcinoma, Skin Appendage; Skin Neoplasms; Sweat Glands; Mucins
PubMed: 37903397
DOI: 10.12788/cutis.0856 -
MSphere Apr 2024Human cutaneous squamous cell carcinomas (SCCs) and actinic keratoses (AK) display microbial dysbiosis with an enrichment of staphylococcal species, which have been...
UNLABELLED
Human cutaneous squamous cell carcinomas (SCCs) and actinic keratoses (AK) display microbial dysbiosis with an enrichment of staphylococcal species, which have been implicated in AK and SCC progression. SCCs are common in both felines and canines and are often diagnosed at late stages leading to high disease morbidity and mortality rates. Although recent studies support the involvement of the skin microbiome in AK and SCC progression in humans, there is no knowledge of this in companion animals. Here, we provide microbiome data for SCC in cats and dogs using culture-independent molecular profiling and show a significant decrease in microbial alpha diversity on SCC lesions compared to normal skin ( 0.05). Similar to human skin cancer, SCC samples had an elevated abundance of staphylococci relative to normal skin-50% (6/12) had >50% staphylococci, as did 16% (4/25) of perilesional samples. Analysis of at the species level revealed an enrichment of the pathogenic species in cat SCC samples, a higher prevalence of in dogs, and a higher abundance of compared to normal skin in both companion animals. Additionally, a comparison of previously published human SCC and perilesional samples against the present pet samples revealed that was the most prevalent genera across human and companion animals for both sample types. Similarities between the microbial profile of human and cat/dog SCC lesions should facilitate future skin cancer research.
IMPORTANCE
The progression of precancerous actinic keratosis lesions (AK) to cutaneous squamous cell carcinoma (SCC) is poorly understood in humans and companion animals, despite causing a significant burden of disease. Recent studies have revealed that the microbiota may play a significant role in disease progression. has been found in high abundance on AK and SCC lesions, where it secretes DNA-damaging toxins, which could potentiate tumorigenesis. Currently, a suitable animal model to investigate this relationship is lacking. Thus, we examined the microbiome of cutaneous SCC in pets, revealing similarities to humans, with increased staphylococci and reduced commensals on SCC lesions and peri-lesional skin compared to normal skin. Two genera that were in abundance in SCC samples have also been found in human oral SCC lesions. These findings suggest the potential suitability of pets as a model for studying microbiome-related skin cancer progression.
Topics: Cats; Dogs; Animals; Carcinoma, Squamous Cell; Microbiota; Skin Neoplasms; Skin; Cat Diseases; Staphylococcus; Dog Diseases; Keratosis, Actinic
PubMed: 38530017
DOI: 10.1128/msphere.00555-23 -
Medicina (Kaunas, Lithuania) Feb 2022Skin nodular lesion are really frequent, but rapidly growing ones needs to be quickly removed since they can hide really aggressive skin tumor. Among malignant lesion...
Skin nodular lesion are really frequent, but rapidly growing ones needs to be quickly removed since they can hide really aggressive skin tumor. Among malignant lesion Merkel cell carcinoma arise. It is a rare neuroendocrine skin tumor highly aggressive, not easy to diagnose at first stage, since at first diagnosis it is already widespreading all over the body. In order to renew interest in this letal skin tumori is mandatory to remind high risk population which include elderly people, white skin, chronically exposed to UV immunocompromised. Our unhappy case was described to increase awareness on this kind of skin tumor, since new drug appeared in the market can give an hope to these patients.
Topics: Aged; Carcinoma, Merkel Cell; Humans; Skin; Skin Neoplasms
PubMed: 35208592
DOI: 10.3390/medicina58020269 -
Psychiatria Danubina Dec 2021The aim of this study was to evaluate the incidence and clinical features of non-melanoma tumors of the head and neck, as well as the validity of surgical therapy in...
BACKGROUND
The aim of this study was to evaluate the incidence and clinical features of non-melanoma tumors of the head and neck, as well as the validity of surgical therapy in their treatment.
SUBJECTS AND METHODS
The study included 530 patients who were operated in the Otorhinolaryngology department of the Livno County Hospital.
RESULTS
In 295 cases (65.1%), it was basal cell carcinoma of the skin and was followed by squamous cell carcinoma of the skin, in 119 cases (29.9%) while the remaining 5% of cases referred to other non-melanoma skin carcinomas. Statistically significant, the most common non-melanoma skin carcinoma was basal cell carcinoma (χ=625,67; df=4; p<0.01). The most co mmon localization was the skin of the nose (24.2%), which proved to be statistically significant (χ=290.824; df=5; p=0.00). All patients underwent classic surgery, and in 358 cases (89.5%) the tumor was completely removed, while in 40 cases (10.5%) the tumor was partially removed which proved to be statistically significant (χ=254,08; df=1; p=0.00).
CONCLUSIONS
The results of the study fully confirm the assertion that classical surgery is the method of choice in the treatment of non-melanoma skin cancers and in the vast majority it is proven to be sufficient.
Topics: Carcinoma, Basal Cell; Carcinoma, Squamous Cell; Humans; Retrospective Studies; Skin; Skin Neoplasms
PubMed: 35150500
DOI: No ID Found