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1.
Skin Res Technol ; 30(7): e13774, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38953214

RESUMO

OBJECTIVE: Observational studies have identified a dual effect of circulating inflammatory proteins and immune cells on cancer progression. However, the specific mechanisms of action have not been clarified in the exacerbation of cutaneous-origin tumors. Therefore, this study aims to investigate whether the causal relationship between circulating inflammatory factors and basal cell carcinoma (BCC), cutaneous malignant melanoma (SKCM), and cutaneous squamous cell carcinoma (cSCC) is regulated by immune cells. METHODS: This study employed the Two-Sample Mendelian Randomization (TSMR) approach to investigate the causal relationships between 91 circulating inflammatory factors and three prevalent types of skin cancer from a genetic perspective. Bayesian Weighted Mendelian Randomization (BWMR) was also used to validate correlation and reverse MR to assess inverse relationships. Subsequent sensitivity analyses were conducted to limit the impact of heterogeneity and pleiotropy. Finally, the two-step Mendelian Randomization (two-step MR) method was utilized to ascertain the mediating effects of specific immune cell traits in the causal pathways linking circulating inflammatory factors with BCC, SKCM, and cSCC. RESULTS: The Inverse Variance Weighted (IVW) method and the Bayesian Weighted Algorithm collectively identified nine inflammatory factors causally associated with BCC, SKCM, and cSCC. The results from Cochran's Q test, mendelian randomization pleiotropy residual sum and outlier (MR-PRESSO), and MR-Egger intercept were not statistically significant (p < 0.05). Additionally, the proportions mediated by CD4+ CD8dim T cell %leukocyte, CD4-CD8-Natural Killer T %T cell, and CD20 on IgD-CD38-B cell for FIt3L, CCL4, and OSM were 9.26%, 8.96%, and 10.16%, respectively. CONCLUSION: Immune cell levels potentially play a role in the modulation process between circulating inflammatory proteins and cutaneous-origin exacerbated tumors. This finding offers a new perspective for the in-depth exploration of cutaneous malignancies.


Assuntos
Carcinoma Basocelular , Carcinoma de Células Escamosas , Melanoma , Análise da Randomização Mendeliana , Neoplasias Cutâneas , Humanos , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/imunologia , Melanoma/genética , Melanoma/imunologia , Melanoma/sangue , Carcinoma Basocelular/genética , Carcinoma Basocelular/imunologia , Carcinoma Basocelular/sangue , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/imunologia , Carcinoma de Células Escamosas/patologia , Teorema de Bayes , Melanoma Maligno Cutâneo
2.
J Drugs Dermatol ; 20(2): 156-165, 2021 02 01.
Artigo em Inglês | MEDLINE | ID: mdl-33538567

RESUMO

Basal cell carcinoma (BCC) is the most common malignancy in fair-skinned populations. Most cases are successfully treated with surgery, but in advanced BCC—including locally advanced BCC and metastatic BCC—surgery is likely to result in substantial morbidity or unlikely to be effective. In those patients, the systemic Hedgehog inhibitors (HHIs) sonidegib and vismodegib are the only approved pharmacologic treatment option. Although a number of clinical studies highlight the similarities and differences between the two HHIs, no head-to-head clinical comparison is available. Results from the pivotal BOLT and ERIVANCE clinical studies for sonidegib and vismodegib, respectively, demonstrate similar efficacy measured by objective response rate, complete response rate, and histologic tumor subtype. Safety results for both studies are comparable with similar common adverse events reported for muscle spasms, alopecia, and dysgeusia. A notable difference between sonidegib and vismodegib is their respective pharmacokinetic profiles with sonidegib reaching peak concentration in plasma within 2–4 hours of dosing and steady state in plasma achieved by week 17 of treatment, while vismodegib reaches peak plasma concentration approximately 2 days after a single dose and steady state within 21 days of repeated dosing. This review compares efficacy, safety, and pharmacokinetics of sonidegib and vismodegib based on published literature to date. J Drugs Dermatol. 2021;20(2):156-165. doi:10.36849/JDD.5657 THIS ARTICLE HAD BEEN MADE AVAILABLE FREE OF CHARGE. PLEASE SCROLL DOWN TO ACCESS THE FULL TEXT OF THIS ARTICLE WITHOUT LOGGING IN. NO PURCHASE NECESSARY. PLEASE CONTACT THE PUBLISHER WITH ANY QUESTIONS.


Assuntos
Anilidas/administração & dosagem , Compostos de Bifenilo/administração & dosagem , Carcinoma Basocelular/tratamento farmacológico , Proteínas Hedgehog/antagonistas & inibidores , Piridinas/administração & dosagem , Neoplasias Cutâneas/tratamento farmacológico , Alopecia/induzido quimicamente , Alopecia/epidemiologia , Anilidas/efeitos adversos , Anilidas/farmacocinética , Compostos de Bifenilo/efeitos adversos , Compostos de Bifenilo/farmacocinética , Carcinoma Basocelular/sangue , Carcinoma Basocelular/mortalidade , Carcinoma Basocelular/patologia , Ensaios Clínicos Fase II como Assunto , Disgeusia/induzido quimicamente , Disgeusia/epidemiologia , Proteínas Hedgehog/metabolismo , Humanos , Estudos Multicêntricos como Assunto , Intervalo Livre de Progressão , Piridinas/efeitos adversos , Piridinas/farmacocinética , Ensaios Clínicos Controlados Aleatórios como Assunto , Transdução de Sinais/efeitos dos fármacos , Neoplasias Cutâneas/sangue , Neoplasias Cutâneas/mortalidade , Neoplasias Cutâneas/patologia , Espasmo/induzido quimicamente , Espasmo/epidemiologia
3.
Cutan Ocul Toxicol ; 36(3): 278-282, 2017 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-28067074

RESUMO

BACKGROUND: The aim of this study is to measure and compare the dynamic thiol/disulphide homeostasis of patients with basal cell carcinoma and healthy subjects with a newly developed and original method. OBJECTIVE: Thirty four patients attending our outpatient clinic and clinically and histopathologically diagnosed as nodular basal cell carcinoma, and age and gender matched 30 healthy individuals have been involved in the study. Thiol/disulphide homeostasis tests have been measured with a novel automatic spectrophotometric method developed and the results have been compared statistically. RESULTS: Serum native thiol and disulphide levels in the patient and control group show a considerable variance statistically (p = 0.028, 0.039, respectively). Total thiol levels do not reveal a considerable variation (p = 0.094). Disulphide/native thiol ratios and native thiol/total thiol ratios also show a considerable variance statistically (p = 0.012, 0.013, 0.010, respectively). CONCLUSIONS: Thiol disulphide homeostasis in patients with basal cell carcinoma alters in the way that disulphide gets lower and thiols get higher. Thiol/disulphide level is likely to have a role in basal cell carcinoma pathogenesis.


Assuntos
Carcinoma Basocelular/sangue , Dissulfetos/sangue , Neoplasias Cutâneas/sangue , Compostos de Sulfidrila/sangue , Idoso , Feminino , Homeostase , Humanos , Masculino , Pessoa de Meia-Idade
5.
Arch Dermatol Res ; 316(6): 214, 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38787420

RESUMO

We aimed to unveil the underlying pathogenic mechanisms of skin cancer in relation to metabolic factors and pathway mechanisms. This study utilized the TwoSample Mendelian randomization (MR) method to investigate the causal relationship between 1400 plasma metabolites and skin cancer. The primary method employed was the inverse variance weighting (IVW). Through IVW analysis, we found 105 plasma metabolites associated with Basal Cell Carcinoma (BCC), with the highest association observed for Prolylglycine levels (OR [95% CI]: 1.1902 [1.0274, 1.3788]). For Malignant Melanoma of Skin (MSS), 68 plasma metabolites were linked, with the highest causal relationship seen for 3-Hydroxybutyrate levels (OR [95% CI]: 1.0030 [1.0013, 1.0048]). Regarding actinic keratosis (AK), and the highest association observed for Hexadecadienoate (16:2n6) levels (OR [95% CI]: 1.3302 [1.0333, 1.7125]). Glycerol to palmitoylcarnitine (16: n6) levels (OR [95% CI]: 1.3302 [1.0333, 1.125]) were found to be significant for BCC and AK. Palmitoylcarnitine (C16) had the most positive causal effect for BCC (OR [95% CI]: 1.1777 [1.0493, 1.3218]), while 5-hydroxy-2-methylpyridine sulfate levels had the highest effect for AK (OR [95% CI]: 1.1788 [1.0295, 1.3498]). And 4-guanidinobutanoate levels had the largest positive causal effect (OR [95% CI]: 1.0857 [1.0417, 1.1317]) for BCC, and X-11880 levels for MSS (OR [95% CI]: 1.0013 [1.0000, 1.0025]). The study revealed a positive association between hereditary Glycerol to palmitoylcarnitine (C16) and 5-hydroxy-2-methylpyridine sulfate levels with the risk of developing BCC and AK. Additionally, 4-guanidinobutanoate levels and X 11880 levels were found to be positively associated with the risk of BCC and MMS.


Assuntos
Carcinoma Basocelular , Análise da Randomização Mendeliana , Neoplasias Cutâneas , Humanos , Neoplasias Cutâneas/sangue , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/epidemiologia , Carcinoma Basocelular/sangue , Carcinoma Basocelular/genética , Carcinoma Basocelular/epidemiologia , Melanoma/sangue , Melanoma/genética , Melanoma/epidemiologia , Ceratose Actínica/sangue , Ceratose Actínica/genética , Ácido 3-Hidroxibutírico/sangue , Predisposição Genética para Doença , Melanoma Maligno Cutâneo
6.
Lasers Med Sci ; 28(3): 997-1005, 2013 May.
Artigo em Inglês | MEDLINE | ID: mdl-22926533

RESUMO

Methyl aminolevulinate photodynamic therapy (MAL-PDT) (a topical treatment used for a number of precancerous skin conditions) utilizes the combined interaction of a photosensitizer (protoporphyrin IX (PpIX)), light of the appropriate wavelength, and molecular oxygen to produce singlet oxygen and other reactive oxygen species which induce cell death. During treatment, localized oxygen depletion occurs and is thought to contribute to decreased efficacy. The aim of this study was to investigate whether an oxygen pressure injection (OPI) device had an effect on localized oxygen saturation levels and/or PpIX fluorescence of skin lesions during MAL-PDT. This study employed an OPI device to apply oxygen under pressure to the skin lesions of patients undergoing standard MAL-PDT. Optical reflectance spectrometry and fluorescence imaging were used to noninvasively monitor the localized oxygen saturation and PpIX fluorescence of the treatment area, respectively. No significant changes in oxygen saturation were observed when these data were combined for the group with OPI and compared to the group that received standard MAL-PDT without OPI. Additionally, no significant difference in PpIX photobleaching or clinical outcome at 3 months between the groups of patients was observed, although the group that received standard MAL-PDT demonstrated a significant increase (p<0.05) in PpIX fluorescence initially and both groups produced a significant decrease (p<0.05) after light irradiation. In conclusion, with this sample size, this OPI device was not found to be an effective method with which to improve tissue oxygenation during MAL-PDT. Further investigation is therefore required to find a more effective method of MAL-PDT enhancement.


Assuntos
Ácido Aminolevulínico/análogos & derivados , Oxigênio/administração & dosagem , Fotoquimioterapia/métodos , Fármacos Fotossensibilizantes/uso terapêutico , Lesões Pré-Cancerosas/tratamento farmacológico , Neoplasias Cutâneas/tratamento farmacológico , Ácido Aminolevulínico/uso terapêutico , Doença de Bowen/sangue , Doença de Bowen/tratamento farmacológico , Carcinoma Basocelular/sangue , Carcinoma Basocelular/tratamento farmacológico , Humanos , Ceratose Actínica/sangue , Ceratose Actínica/tratamento farmacológico , Oxigênio/sangue , Lesões Pré-Cancerosas/sangue , Pressão , Protoporfirinas/uso terapêutico , Neoplasias Cutâneas/sangue
7.
Nutrients ; 14(16)2022 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-36014865

RESUMO

Ultraviolet radiation is known as one of the major contributors to skin malignancies, including basal cell carcinoma (BCC), which is the most common type of skin cancer. It is a heterogeneous tumor, which presents with various types that are stratified into low- and high-risk tumors. Sunlight is important for overall health and vitamin D synthesis in the skin, whereas deviations from the optimal level of vitamin D are shown to be associated with the risk of the development of BCC. The accumulating evidence suggests the ability of vitamin D to antagonize the Sonic Hedgehog (SHH) signaling, the key tumor pathway, and play a protective role in the development of BCC. Additionally, a vitamin D binding protein (DBP) is shown to be implicated in the complex regulation of vitamin D. Here, we aimed to explore serum vitamin D in patients with different primary and recurrent BCC of the head and neck and investigate cutaneous DBP and SHH indices, confirmed immunohistochemically in these subjects. According to the results, 94.9% of the Latvian cohort of BCC patients were found to be deficient in vitamin D. No significant differences in serum vitamin D levels were found between genders, primary and recurrent tumors, and different types of BCC. Serum vitamin D was inversely associated with tumor size. Susceptible male individuals with low blood vitamin D levels were recognized at risk of developing aggressive and recurrent BCC confirmed by the use of hierarchical clustering analysis. In smaller tumors with a favorable course, such as superficial and nodular BCC, the association between high DBP and low SHH tissue expression was found, providing supportive evidence of the existence of a link between vitamin D, proteins involved in its metabolism, as exemplified by the DBP and SHH signaling pathway. The assumption of a deficiency in the protective effect of vitamin D in patients with high-risk BCCs was proposed in low DBP and high SHH tissue indices. New extensions to existing knowledge and characterization of the BCC signaling pathways and their cross-talk with vitamin D are warranted when searching for a preferential effect of vitamin D on skin cancer.


Assuntos
Carcinoma Basocelular , Proteínas Hedgehog , Neoplasias Cutâneas , Proteína de Ligação a Vitamina D , Vitamina D , Carcinoma Basocelular/sangue , Carcinoma Basocelular/etiologia , Carcinoma Basocelular/genética , Carcinoma Basocelular/metabolismo , Feminino , Proteínas Hedgehog/genética , Proteínas Hedgehog/metabolismo , Humanos , Letônia , Masculino , Neoplasias Cutâneas/sangue , Neoplasias Cutâneas/etiologia , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/metabolismo , Raios Ultravioleta/efeitos adversos , Vitamina D/sangue , Proteína de Ligação a Vitamina D/genética , Proteína de Ligação a Vitamina D/metabolismo
8.
Genome Med ; 13(1): 19, 2021 02 06.
Artigo em Inglês | MEDLINE | ID: mdl-33549134

RESUMO

BACKGROUND: Basal cell carcinoma (BCC) of the skin is the most common form of human cancer, with more than 90% of tumours presenting with clear genetic activation of the Hedgehog pathway. However, polygenic risk factors affecting mechanisms such as DNA repair and cell cycle checkpoints or which modulate the tumour microenvironment or host immune system play significant roles in determining whether genetic mutations culminate in BCC development. We set out to define background genetic factors that play a role in influencing BCC susceptibility via promoting or suppressing the effects of oncogenic drivers of BCC. METHODS: We performed genome-wide association studies (GWAS) on 17,416 cases and 375,455 controls. We subsequently performed statistical analysis by integrating data from population-based genetic studies of multi-omics data, including blood- and skin-specific expression quantitative trait loci and methylation quantitative trait loci, thereby defining a list of functionally relevant candidate BCC susceptibility genes from our GWAS loci. We also constructed a local GWAS functional interaction network (consisting of GWAS nearest genes) and another functional interaction network, consisting specifically of candidate BCC susceptibility genes. RESULTS: A total of 71 GWAS loci and 46 functional candidate BCC susceptibility genes were identified. Increased risk of BCC was associated with the decreased expression of 26 susceptibility genes and increased expression of 20 susceptibility genes. Pathway analysis of the functional candidate gene regulatory network revealed strong enrichment for cell cycle, cell death, and immune regulation processes, with a global enrichment of genes and proteins linked to TReg cell biology. CONCLUSIONS: Our genome-wide association analyses and functional interaction network analysis reveal an enrichment of risk variants that function in an immunosuppressive regulatory network, likely hindering cancer immune surveillance and effective antitumour immunity.


Assuntos
Carcinoma Basocelular/genética , Carcinoma Basocelular/imunologia , Redes Reguladoras de Genes , Predisposição Genética para Doença , Neoplasias Cutâneas/genética , Neoplasias Cutâneas/imunologia , Linfócitos T Reguladores/imunologia , Bancos de Espécimes Biológicos , Carcinoma Basocelular/sangue , Metilação de DNA/genética , Regulação Neoplásica da Expressão Gênica , Estudo de Associação Genômica Ampla , Humanos , Análise da Randomização Mendeliana , Especificidade de Órgãos/genética , Mapas de Interação de Proteínas/genética , Locos de Características Quantitativas/genética , Neoplasias Cutâneas/sangue
9.
Arch Dermatol Res ; 313(5): 373-380, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-32772162

RESUMO

Cytokines involved in inflammatory and immune response have been associated with risk for development of basal cell carcinoma (BCC). In this study, three functional DNA polymorphisms affecting gene expression were investigated in 54 BCC patients and 111 healthy controls: interleukin-1b (IL-1b) +3953C/T, interleukin-10 (IL-10) - 1082G/A and angiotensin-converting enzyme (ACE) insertion/deletion (I/D) polymorphisms. Significant increase of the variant alleles was observed in IL-10 - 1082G (P = 0.019) and in ACE D (P = 0.003) in BCC patients in comparison to controls. Multivariate logistic regression models evaluated the contribution of homozygous and heterozygous variant polymorphisms to the risk for BCC development. The studied polymorphisms influencing the expression of IL-10 and ACE genes were recognized as potential predictive factors for BCC. These findings suggest a possible molecular mechanism leading to BCC development that is likely to involve the activation of angiotensin receptors in combination with increased plasma levels of IL-10 in patients.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma Basocelular/genética , Interleucina-10/genética , Peptidil Dipeptidase A/genética , Neoplasias Cutâneas/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Angiotensinas/metabolismo , Biomarcadores Tumorais/sangue , Carcinoma Basocelular/sangue , Carcinoma Basocelular/diagnóstico , Estudos de Casos e Controles , Feminino , Regulação Neoplásica da Expressão Gênica , Predisposição Genética para Doença , Voluntários Saudáveis , Humanos , Interleucina-10/sangue , Interleucina-10/metabolismo , Masculino , Pessoa de Meia-Idade , Peptidil Dipeptidase A/metabolismo , Polimorfismo de Nucleotídeo Único , Transdução de Sinais/genética , Neoplasias Cutâneas/sangue , Neoplasias Cutâneas/diagnóstico , Adulto Jovem
10.
Sci Rep ; 10(1): 13151, 2020 08 04.
Artigo em Inglês | MEDLINE | ID: mdl-32753685

RESUMO

Sun exposure is a major environmental risk factor for skin cancers and is also an important source of vitamin D. However, while experimental evidence suggests that vitamin D may have a protective effect on skin cancer risk, epidemiologic studies investigating the influence of 25-hydroxyvitamin D (25(OH)D) level and/or vitamin D intake on skin cancer risk are conflicting. A systematic review and dose-response meta-analyses of prospective studies was conducted to clarify these associations. Relevant studies were identified by searching the PubMed database up to 30th August 2019. Random effects dose-response meta-analyses were used to estimate summary relative risks (SRRs) and 95% confidence intervals (CIs). Overall, thirteen prospective studies were included. Circulating level of 25(OH)D was associated with higher risks of melanoma (SRR (95% CI) per 30 nmol = 1.42 (1.17-1.72)) and keratinocyte cancer (KC) (SRR (95% CI) per 30 nmol/L = 1.30 (1.13-1.49)). The SRR (95% CI) per 30 nmol/L increase in 25(OH) D level was 1.41 (1.19-1.67), and 1.57 (0.64-3.86), for basal cell carcinomas (BCCs) and squamous cell carcinomas (SCCs), respectively. However, while we found that vitamin D intake (from diet, supplemental and total) was not associated with risks of melanoma and SCC, vitamin D intake was associated with slightly increased BCC risk, albeit with no heterogeneity across skin cancer type. This meta-analysis suggests positive associations between circulating 25(OH)D level and risk of melanoma and KC, however, this finding is most likely confounded by sun exposure. We found no associations between vitamin D intake skin cancers, except positive associations with BCC risk.


Assuntos
Carcinoma Basocelular , Neoplasias Cutâneas , Vitamina D/análogos & derivados , Carcinoma Basocelular/sangue , Carcinoma Basocelular/epidemiologia , Carcinoma Basocelular/prevenção & controle , Relação Dose-Resposta a Droga , Humanos , Estudos Prospectivos , Fatores de Risco , Neoplasias Cutâneas/sangue , Neoplasias Cutâneas/epidemiologia , Neoplasias Cutâneas/prevenção & controle , Vitamina D/sangue , Vitamina D/uso terapêutico
11.
Cancer Epidemiol Biomarkers Prev ; 18(4): 1167-73, 2009 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-19336544

RESUMO

BACKGROUND: Antioxidant nutrients can help prevent skin damage caused by ultraviolet radiation from sunlight, but it is not clear whether serum concentrations of such nutrients influence skin cancer risk. METHODS: We carried out a prospective study of the associations between serum concentrations of antioxidant nutrients and incidence (person-based and tumor-based) of basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) of the skin among a random subsample of 485 adults from an Australian community. Participants were divided into thirds, ranked according to their serum concentrations of carotenoids, alpha-tocopherol, and selenium measured in 1996 and were monitored for incident, histologically confirmed BCC and SCC tumors until 2004. RESULTS: Although there were no associations between baseline serum carotenoids or alpha-tocopherol concentrations and incidence of BCC or SCC, baseline serum selenium concentrations showed strong inverse associations with both BCC and SCC tumor incidence. Compared with participants with lowest selenium concentrations at baseline (0.4-1.0 micromol/L), those with the highest serum selenium concentrations (1.3-2.8 micromol/L) had a decreased incidence of BCC tumors (multivariate relative risk, 0.43; 95% confidence interval, 0.21-0.86; P(trend) = 0.02) and SCC tumors (multivariate relative risk, 0.36; 95% confidence interval, 0.15-0.82; P(trend) = 0.02). CONCLUSION: Relatively high serum selenium concentrations are associated with an approximately 60% decrease in subsequent tumor incidence of both BCC and SCC, whereas serum concentrations of carotenoids or alpha-tocopherol are not associated with later skin cancer incidence. A possible U-shaped association between serum selenium concentrations and SCC of the skin needs confirmation.


Assuntos
Antioxidantes/metabolismo , Biomarcadores Tumorais/sangue , Carotenoides/sangue , Compostos de Selênio/sangue , Neoplasias Cutâneas/epidemiologia , alfa-Tocoferol/sangue , Idoso , Austrália/epidemiologia , Carcinoma Basocelular/sangue , Carcinoma Basocelular/epidemiologia , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/epidemiologia , Estudos de Coortes , Feminino , Seguimentos , Humanos , Incidência , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Medição de Risco , Neoplasias Cutâneas/sangue
12.
Iran J Immunol ; 16(1): 53-61, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30864555

RESUMO

BACKGROUND: Interleukin 17 (IL-17) is a pro-inflammatory cytokine that plays an important role in cancer pathogenesis. OBJECTIVE: To investigate the association of two IL-17 gene polymorphisms (rs2275913 and rs763780), as well as IL-17 serum levels with susceptibility to Basal Cell Carcinoma (BCC) of skin. METHODS: Two hundred subjects with BCC and 200 healthy controls were recruited. DNA was extracted from peripheral blood leukocytes and genotypes were determined using PCR-RFLP methods. Serum levels were assessed by ELISA. RESULTS: At position rs2275913 in IL-17A, the frequencies of GG, AG and AA genotypes were 99 (49.5%), 76 (38%) and 25 (12.5%) in patients and 97 (48.5%), 84 (42%) and 19 (9.5%) in the control group. The distribution of AA, GA and GG genotypes at position rs763780 in IL-17F were 166 (83%), 34 (17%) and 0 (0%) in patients and 158 (79%), 40 (20%) and 2 (1%) in the control group. Haplotype analysis by Arlequin software package revealed that GA haplotype was the most frequent haplotype in both groups. No significant differences were found in alleles, genotypes, and haplotypes frequencies between study groups at both positions (P>0.05). While no difference in IL-17 serum levels was observed between individuals with different genotypes, statistical analysis showed higher IL-17A serum levels, but not IL-17F, in patients compared to controls (0.65 ± 0.11 and 0.03 ± 0.02 pg/ml), respectively, (P<0.001). CONCLUSION: Our findings do not support the association of rs763780 and rs2275913 gene polymorphisms in IL-17gene with susceptibility of Iranians with BCC. Increased IL-17A serum levels may still play a role in pathogenesis of BCC.


Assuntos
Carcinoma Basocelular/sangue , Carcinoma Basocelular/genética , Interleucina-17/sangue , Interleucina-17/genética , Polimorfismo de Nucleotídeo Único , Neoplasias Cutâneas/sangue , Neoplasias Cutâneas/genética , Idoso , Alelos , Estudos de Casos e Controles , Ensaio de Imunoadsorção Enzimática , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Razão de Chances
13.
Artigo em Inglês | MEDLINE | ID: mdl-31252537

RESUMO

BACKGROUND: Development of nonmelanoma skin cancers (NMSCs) has been associated with certain risk factors, but studies of the association between ABO blood group and NMSCs have been rare and inconclusive. The aim of this study was to assess the association of the previously known risk factors and blood group as a new potential risk factor in NMSCs. METHODS: The study included 401 patients, 202 men, and 199 women, which included 367 diagnosed cases of basal cell carcinoma and 148 diagnosed cases of squamous cell carcinoma. The control group consisted of 438 subjects, 198 men, and 240 women. A standardized questionnaire adapted for this targeted study was used. The relation between the dependent variable (NMSCs) and independent variables was investigated by logistic regression. RESULTS: Compared to the non AB blood group, the risk of developing NMSCs was significantly higher in the AB blood group (MOR = 2.28; 95% CI = 1.41-3.69). We established a logistic model that could best describe the probability of NMSCs development. CONCLUSION: Study results are expected to instigate basic research into the role of A and B antigens in normal skin epithelium, NMSCs etiopathogenesis, possible effect on metastatic potential and disease prognosis, potential tumor immunotherapy, and targeted detection and prevention in subjects at an increased risk of NMSCs development.


Assuntos
Biomarcadores/sangue , Antígenos de Grupos Sanguíneos/efeitos adversos , Carcinoma Basocelular/sangue , Carcinoma Basocelular/fisiopatologia , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/fisiopatologia , Neoplasias Cutâneas/sangue , Neoplasias Cutâneas/fisiopatologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Basocelular/etiologia , Carcinoma de Células Escamosas/etiologia , Croácia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Neoplasias Cutâneas/etiologia
14.
Arch Dermatol Res ; 311(9): 697-704, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31342143

RESUMO

Basal cell carcinoma (BCC) environment consists of stromal and inflammatory cells which produce variety of cytokines, chemokines and growth factors that may affect tumor behavior. One of the cytokines suggested to be involved in the pathogenesis of BCC is IL-6, which is the upstream element of IL-6/JAK/STAT3 pathway. The correlation between polymorphisms of the genes related to this pathway and cancer risk/prognosis have been previously investigated in several neoplasia, but available data concerning BCC are scarce. In the present study, rs1800795 (-174 G/C) IL-6 gene polymorphism and two polymorphisms in the STAT3 gene, namely rs2293152 (intron 11, C/G) and rs4796793 (-1697, C/G) were assessed in relation to the BCC risk and clinical course. Additionally, IL-6 serum level was assessed in relation to IL-6 genotype and clinical variables. The study included 254 unrelated patients with BCC and of mean age 70.39 ± 11.43 (69.83 ± 12.32 women, 71.03 ± 10.31 men) and 198 healthy, unrelated age- and sex-matched volunteers. IL-6 and STAT3 polymorphisms were analyzed using polymerase chain reaction with sequence-specific primers (SSP-PCR). Serum concentration of IL-6 was measured using the ELISA test. We have found that the presence of C allele in rs1800795 IL-6 gene polymorphism was associated with increased risk of BCC (aOR 1.86; 95% CI 1.22-2.84; p = 0.004). The presence of CC genotype in STAT3 rs2293152 polymorphism was associated with increased BCC risk in recessive model analysis (aOR 3.94; 95% CI 1.59-9.77; p = 0.003). In contrast, the presence of GC genotype in overdominant model was associated with decreased risk of BCC (aOR = 0.24; 95% CI 0.12-0.49; p < 0.0001). The presence of C allele in STAT3 rs2293152 polymorphism was associated with increased risk of BCC (aOR 1.31; 95% CI 1.01-1.69; p = 0.04). The presence of GG genotype in STAT3 rs4796793 polymorphism was associated with increased BCC risk in recessive model analysis (aOR 3.66; 95% CI 1.33-10.10; p = 0.012). The presence of G allele in STAT3 rs4796793 polymorphism was associated with increased risk of BCC (aOR 1.59; 95% CI 1.01-2.49; p = 0.04). IL-6 serum level positively correlated with the tumor size.


Assuntos
Carcinoma Basocelular/genética , Predisposição Genética para Doença , Interleucina-6/genética , Fator de Transcrição STAT3/genética , Neoplasias Cutâneas/genética , Idoso , Idoso de 80 Anos ou mais , Alelos , Carcinoma Basocelular/sangue , Carcinoma Basocelular/patologia , Estudos de Casos e Controles , Feminino , Voluntários Saudáveis , Humanos , Interleucina-6/sangue , Masculino , Pessoa de Meia-Idade , Polônia , Polimorfismo de Nucleotídeo Único , Pele/patologia , Neoplasias Cutâneas/patologia
15.
Melanoma Res ; 18(3): 201-7, 2008 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-18477894

RESUMO

Melanoma inhibitory activity (MIA) protein was identified in significant quantities in primary and metastatic malignant melanomas, where it has an important role in promoting tumor development and progression. Our hypothesis was that MIA serum level will be elevated in patients with metastases or local spreading of the disease before any symptom of such progression is clinically apparent. We compared MIA serum levels in two groups of patients with primary melanoma; those with positive as opposed to those with negative sentinel lymph nodes. In addition, MIA serum levels were studied in two control groups; patients with dysplastic nevi and patients with basal cell carcinoma. A blood sample was obtained from each patient included in the study and MIA levels were assessed using standard enzyme-linked immunosorbent assay method. Patients with histologically positive sentinel lymph nodes, meaning that tumor cells were found in the lymph nodes, had much higher mean MIA values than any other patient group considered in this study. With mean value of 14.53 ng/ml, it was almost twice as high as mean MIA value in patients with histologically negative sentinel lymph nodes (7.32 ng/ml) and more than twice as high than any of the two control groups (P<0.001). However, neither the classification by Clarke nor the classification by Breslow could be used to distinguish patients with positive sentinel lymph nodes from those with negative sentinel lymph nodes. In our opinion, MIA serum level is the ideal test for screening the tumor spread to sentinel lymph nodes.


Assuntos
Proteínas da Matriz Extracelular/sangue , Melanoma/sangue , Melanoma/diagnóstico , Proteínas de Neoplasias/sangue , Neoplasias Cutâneas/sangue , Neoplasias Cutâneas/diagnóstico , Adulto , Idoso , Biomarcadores Tumorais/análise , Biomarcadores Tumorais/sangue , Carcinoma Basocelular/sangue , Carcinoma Basocelular/patologia , Síndrome do Nevo Displásico/sangue , Feminino , Humanos , Metástase Linfática , Masculino , Melanoma/patologia , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Prognóstico , Valores de Referência , Sensibilidade e Especificidade , Biópsia de Linfonodo Sentinela , Neoplasias Cutâneas/patologia
16.
Dis Esophagus ; 21(5): 395-401, 2008.
Artigo em Inglês | MEDLINE | ID: mdl-19125792

RESUMO

The malignant transformation of esophageal mucosa is a progressive process, which includes basal cell hyperplasia, dysplasia, carcinoma in situ, and invasive esophageal squamous cell carcinoma (ESCC). The objectives of this study were to prove the relationship of squamous cell carcinoma antigen 2 (SCCA2) mRNA expression in peripheral blood with non-malignant lesion, premalignant lesion, and carcinoma of the esophagus at the same assay, as well as to evaluate whether or not SCCA2 mRNA expression in peripheral blood may be a biomarker for monitoring the premalignant lesion of the disease. The subjects consisted of 50 patients with basal cell hyperplasia, 50 patients with dysplasia, 50 patients with ESCC (12 carcinoma in situ, 38 carcinoma in invasive stage), and 50 controls who were pathologically diagnosed to be normal and whose esophageal mucosa were stained brown by iodine. All the subjects are residents of Feicheng, China, which is considered an area with a high incidence of esophageal cancer. All subjects were diagnosed by two separate histopathologists, and the expression of SCCA2 mRNA in peripheral blood was detected by semiquantitative reverse transcription-polymerase chain reaction (RT-PCR). Furthermore, SCCA2 concentration in the serum was measured using an enzyme-linked immunosorbent assay (ELISA). In the cancer group, SCCA2 mRNA expression was also detected in 20 tissues of esophageal cancer. By using the band intensity ratios of SCCA2 to beta-actin, with a positive cut-off value of > or = 0.4, the positive rates of the SCCA2 mRNA expression in peripheral blood were found to be 82% (41/50), 60% (30/50), 48% (24/50), and 36% (18/50) in the cancer, dysplasia, basal cell hyperplasia, and control groups, respectively. The positive rate of the cancer group was significantly different from the three other groups (P < 0.05), and there was also a significant difference in the SCCA2 mRNA expression between the dysplasia group and the control group (chi(2)=5.769, P= 0.016). In the multinomial logistic regression analysis, the odds ratios (ORs) were 1.71 [95% confidence interval (95% CI), 0.73-3.99] in the basal cell hyperplasia group, 2.77 (95% CI, 1.14-6.71) in the dysplasia group, and 7.87 (95% CI, 2.88-21.55) in the cancer group after being adjusted for age, gender, smoking index, drinking index, and family history of esophageal cancer. The SCCA2 mRNA expression in peripheral blood was then divided into different grades according to the band intensity ratios of SCCA2 to beta-actin. By using a positive cut-off value of > or = 0.4, the testing sensitivities in the basal cell hyperplasia, dysplasia, and cancer groups were found to be 48%, 60%, and 82%, respectively, with the same testing specificity at 64%. On the other hand, SCCA2 mRNA expression in peripheral blood had a 97.5% agreement with that in tissue, and there was a significant correlation between the ELISA SCCA2 levels in the serum and the SCCA2 mRNA expression levels in the peripheral blood (r= 0.80, P= 0.01). The results indicate that SCCA2 mRNA expression in peripheral blood is linked with the different stages of esophageal pathological changes, despite the fact that SCCA2 mRNA was not a biomarker for screening early esophageal cancer. This knowledge may be useful in monitoring the processes of change that occur in esophageal premalignant lesions among subjects who live in a high-incidence area.


Assuntos
Antígenos de Neoplasias/sangue , Biomarcadores Tumorais/sangue , Carcinoma de Células Escamosas/patologia , Neoplasias Esofágicas/sangue , Neoplasias Esofágicas/patologia , Lesões Pré-Cancerosas/sangue , Lesões Pré-Cancerosas/patologia , Serpinas/sangue , Adulto , Idoso , Carcinoma Basocelular/sangue , Carcinoma Basocelular/genética , Carcinoma Basocelular/patologia , Carcinoma de Células Escamosas/sangue , Carcinoma de Células Escamosas/genética , Estudos de Casos e Controles , Intervalos de Confiança , Progressão da Doença , Detecção Precoce de Câncer , Ensaio de Imunoadsorção Enzimática , Neoplasias Esofágicas/genética , Feminino , Seguimentos , Regulação Neoplásica da Expressão Gênica , Humanos , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Probabilidade , RNA Mensageiro/análise , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Medição de Risco , Sensibilidade e Especificidade
17.
Clin Nutr ESPEN ; 23: 107-111, 2018 02.
Artigo em Inglês | MEDLINE | ID: mdl-29460784

RESUMO

BACKGROUND: Skin cancers are the most prevalent malignancy worldwide and Basal Cell Carcinoma (BCC) include the major type of nonmelanoma skin cancers. Fatty acids (FA) have a structural role in cell membranes and play an important role for many physiological and pathological immunologic pathways. Several prospective studies have been conducted on circulating fatty acids and the risk of prostate, breast and other cancers. The present study aimed to determine the saturated fatty acid composition differences of red blood cells (RBCs) in BCC patients and healthy control. METHODS: A hospital-based case-control study was conducted on new cases diagnosed of BCC patients. All subjects completed dietary recalls for dietary assessment. After fatty acids extraction, purification and preparation, gas chromatography was performed. The results were expressed in relative values (percent). RESULTS: Cases had lower RBC levels of Caproic acid (6:0) (P < 0.001), Caprylic acid (8:0) (P = 0.01), Capric acid (10:0) (P = 0.01), Palmitic acid (16:0) (P = 0.02) and higher RBC level of Pentadecanoic acid (15:0) (P = 0.04) and Stearic acid (18:0) (P = 0.01) compared with controls but did not differ in the level of the other primary saturated fatty acids. Saturation Index as defined by Stearic to Oleic acid ratio was significantly lower in BCC patients in comparison with Control group (P = 0.02). CONCLUSION: Here we showed that BCC patient had considerable differences in the SFA profiles in comparison with healthy subjects.


Assuntos
Carcinoma Basocelular/sangue , Membrana Eritrocítica/química , Ácidos Graxos/análise , Carcinoma Basocelular/diagnóstico , Estudos de Casos e Controles , Dieta , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Ácido Palmítico/análise , Tamanho da Amostra , Ácidos Esteáricos/análise
18.
Int J Dermatol ; 57(8): 922-927, 2018 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-29808911

RESUMO

BACKGROUND: Ultraviolet (UV) radiation is the most important environmental risk factor for the development of nonmelanoma skin cancer (NMSC). UV radiation is, however, also vital in the formation of vitamin D in humans. Strict sun protection advised to skin cancer patients may lead to vitamin D deficiency, yet vitamin D may have a protective effect against cancer formation. OBJECTIVES: The primary aim was to determine whether patients with nonmelanoma skin cancer at our institution were vitamin D deficient. METHODS: 25-Hydroxyvitamin D (25[OH]D) levels were determined in 109 patients with a diagnosis of basal cell carcinoma (BCC) and/or squamous cell carcinoma (SCC) during the summer and winter of 2015 at the Tygerberg Academic Hospital in Cape Town, South Africa. Associations between clinical and epidemiological data and the 25(OH)D level results were investigated. Vitamin D deficiency was defined as total 25(OH)D levels <20 ng/mL (<50 nmol/L). RESULTS: It was found that 49.5% of NMSC patients were vitamin D deficient, and 41.3% had insufficient vitamin D levels. Females were more likely than males to be vitamin D deficient (P = 0.047). Winter was significantly associated with vitamin D deficiency, compared to summer (OR = 4.81, 95%CI = 2.09-11.09, P <0.001). Having a previous SCC appeared associated with not being vitamin D deficient (OR = 0.46, 95%CI = 0.20-1.11, P = 0.084). CONCLUSIONS: The findings highlight the need for the development of recommendations and guidelines on sun protection in patients with NMSC, while still ensuring an adequate vitamin D status. High risk factors included winter and female gender.


Assuntos
Carcinoma Basocelular/sangue , Carcinoma de Células Escamosas/sangue , Neoplasias Cutâneas/sangue , Deficiência de Vitamina D/sangue , Deficiência de Vitamina D/epidemiologia , Idoso , Estudos Transversais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estações do Ano , Fatores Sexuais , Pigmentação da Pele , África do Sul/epidemiologia , Protetores Solares/uso terapêutico , Vitamina D/análogos & derivados , Vitamina D/sangue
19.
Eur J Dermatol ; 28(5): 649-653, 2018 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-30355545

RESUMO

BACKGROUND: Sun exposure is critical for vitamin D synthesis and is a major risk factor for the development of non-melanoma skin cancer (NMSC). NMSC is the most common type of cancer in Brazil and coexists with a very high prevalence of vitamin D deficiency. OBJECTIVES: The present study aimed to assess serum 25-hydroxyvitamin D (25[OH]D) concentration in patients with a recent diagnosis of NMSC. MATERIALS & METHODS: The serum 25(OH)D concentration of patients with a histological diagnosis of NMSC, made between September 2016 and September 2017, was measured by chemiluminescence up to 60 days after diagnosis and compared to healthy individuals without NMSC matched by age, sex, BMI, and skin phototype. RESULTS: Forty-one patients with NMSC and 200 healthy controls were evaluated. Most of the patients were men (56.1%) and most had basal cell carcinoma (90.2%). Patients were 67 years old on average (21-87 years) with skin Phototype 2 or 3 (80.6%). Mean serum 25(OH)D concentration in NMSC patients was significantly higher than in healthy controls (p < 0.001). Most of the patients with NMSC (65.9%) had vitamin D deficiency (25[OH]D <30 ng/mL). No association was identified between histological type, time from diagnosis, or a previous history of skin neoplasm and 25(OH)D measurements. CONCLUSION: Patients with recently diagnosed NMSC had significantly higher serum levels of 25(OH)D when compared to healthy controls. On the other hand, most of the NMSC patients were still considered to have vitamin D insufficiency.


Assuntos
Biomarcadores Tumorais/sangue , Carcinoma Basocelular/sangue , Carcinoma de Células Escamosas/sangue , Neoplasias Cutâneas/patologia , Vitamina D/análogos & derivados , Adulto , Idoso , Idoso de 80 Anos ou mais , Análise de Variância , Brasil , Carcinoma Basocelular/patologia , Carcinoma de Células Escamosas/patologia , Estudos de Casos e Controles , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Invasividade Neoplásica/patologia , Estadiamento de Neoplasias , Prognóstico , Valores de Referência , Fatores de Risco , Neoplasias Cutâneas/sangue , Neoplasias Cutâneas/diagnóstico , Estatísticas não Paramétricas , Vitamina D/sangue
20.
J Cancer Res Clin Oncol ; 133(12): 1001-10, 2007 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-17671793

RESUMO

Attenuated total reflectance-Fourier transform infrared (ATR-FTIR) spectroscopy was applied to discriminate the blood samples obtained from healthy people and those with basal cell carcinoma, demonstrating high accuracy while soft independent modeling class analogy (SIMCA) chemometric technique is benefited. It was aimed to classify the normal case and cancer case blood samples through the use of ATR-FTIR spectroscopy as a rapid method while the sample preparation is so easy in comparison with the common pathologic methods. A total of 72 blood samples, including 32 cancer and 40 normal cases, were analyzed in 1,800-900 cm(-1) spectral region. Results showed 97.6% of accuracy being compared with the current clinical methods. Research results were exemplified with comparable data of other classification methods such as principal component analysis (PCA) and Cluster analysis. The residual errors in prediction (REP) of calibration model for normal and cancerous groups in SIMCA method were 0.00362 and 0.00343, respectively.


Assuntos
Carcinoma Basocelular/sangue , Carcinoma Basocelular/diagnóstico , Neoplasias Cutâneas/sangue , Neoplasias Cutâneas/diagnóstico , Espectroscopia de Infravermelho com Transformada de Fourier , Adulto , Análise por Conglomerados , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Análise de Componente Principal , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Espectroscopia de Infravermelho com Transformada de Fourier/instrumentação , Espectroscopia de Infravermelho com Transformada de Fourier/métodos
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