The causal relationship between immune cells mediating FIT3L, CCL4, OSM, and skin-derived deteriorated tumors.

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.

A Review of Hedgehog Inhibitors Sonidegib and Vismodegib for Treatment of Advanced Basal Cell Carcinoma.

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.

Dynamic thiol/disulphide homeostasis in patients with basal cell carcinoma.

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.

Patent blue interferes with the measurement of lipemia index in a patient with sentinel lymph node.

Lipids interfere with absorbance measurements conducted using colorimetric methods. To monitor lipemia, some systems measure absorbance using an analyzer. This report describes a novel case of interference with the lipemia index without lipemia. A 64-year-old woman with giant basal cell carcinoma underwent resection and sentinel lymph node biopsy. The patient had been subcutaneously injected with patent blue during sentinel lymph node resection. After surgery, her serum and urine were yellow-green, and the lipemia index, calculated by measuring absorbance at 658 nm (main wavelength) and 694 nm (secondary wavelength) using a JCA-BM8040 chemistry analyzer, was high. The absorbance spectrum of the patient's serum and patent blue solution were compared to determine the cause of the high lipemia index. The patient's serum and the patent blue solution showed absorption at wavelengths between 540 and 698 nm. Moreover, the absorbance was concentration-dependent for patent blue. These results thus indicated that the patient's serum contained patent blue. Here, we report a case wherein patent blue affected the lipemia index. Thus, it must be noted that patent blue injection may yield inaccurate results when evaluating lipemia index.

Association between blood metabolites and basal cell carcinoma risk: a two-sample Mendelian randomization study.

Background: Circulating metabolites, which play a crucial role in our health, have been reported to be disordered in basal cell carcinoma (BCC). Despite these findings, evidence is still lacking to determine whether these metabolites directly promote or prevent BCC's progression. Therefore, our study aims to examine the potential effects of circulating metabolites on BCC progression. Material and methods: We conducted a two-sample Mendelian randomization (MR) analysis using data from two separate genome-wide association studies (GWAS). The primary study included data for 123 blood metabolites from a GWAS with 25,000 Finnish individuals, while the secondary study had data for 249 blood metabolites from a GWAS with 114,000 UK Biobank participants.GWAS data for BCC were obtained from the UK Biobank for the primary analysis and the FinnGen consortium for the secondary analysis. Sensitivity analyses were performed to assess heterogeneity and pleiotropy. Results: In the primary analysis, significant causal relationships were found between six metabolic traits and BCC with the inverse variance weighted (IVW) method after multiple testing [P < 4 × 10-4 (0.05/123)]. Four metabolic traits were discovered to be significantly linked with BCC in the secondary analysis, with a significance level of P < 2 × 10-4 (0.05/249). We found that all the significant traits are linked to Polyunsaturated Fatty Acids (PUFAs) and their degree of unsaturation. Conclusion: Our research has revealed a direct link between the susceptibility of BCC and Polyunsaturated Fatty Acids and their degree of unsaturation. This discovery implies screening and prevention of BCC.

Causal relationship between genetically determined plasma metabolites and skin cancer: a two-sample Mendelian randomization study.

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.

Effect of an oxygen pressure injection (OPI) device on the oxygen saturation of patients during dermatological methyl aminolevulinate photodynamic therapy.

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.

Serum Vitamin D Levels Explored in the Latvian Cohort of Patients with Basal Cell Carcinoma Linked to the Sonic Hedgehog and Vitamin D Binding Protein Cutaneous Tissue Indices.

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.

Genetic and functional interaction network analysis reveals global enrichment of regulatory T cell genes influencing basal cell carcinoma susceptibility.

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.

Association study indicates combined effect of interleukin-10 and angiotensin-converting enzyme in basal cell carcinoma development.

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.

25-Hydroxyvitamin D status, vitamin D intake, and skin cancer risk: a systematic review and dose-response meta-analysis of prospective studies.

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.

Serum antioxidants and skin cancer risk: an 8-year community-based follow-up study.

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.

Investigation of Interleukin-17 Gene Polymorphisms and Serum Levels in Patients with Basal Cell Carcinoma of the Skin.

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.

Association between Blood Group and Nonmelanoma Skin Cancers (Basal Cell Carcinoma and Squamous Cell Carcinoma).

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.

STAT3 polymorphisms and IL-6 polymorphism are associated with the risk of basal cell carcinoma in patients from northern Poland.

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.

Biological value of melanoma inhibitory activity serum concentration in patients with primary skin melanoma.

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.

An expression of squamous cell carcinoma antigen 2 in peripheral blood within the different stages of esophageal carcinogenesis.

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.

Erythrocyte membrane saturated fatty acids profile in newly diagnosed Basal Cell Carcinoma patients.

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.

Vitamin D status in adult patients with nonmelanoma skin cancer in Cape Town, South Africa: a cross-sectional study.

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.