TNFRSF1B Gene Variants in Clinicopathological Aspects and Prognosis of Patients with Cutaneous Melanoma.

Regulatory T lymphocytes play a critical role in immune regulation and are involved in the aberrant cell elimination by facilitating tumor necrosis factor connection to the TNFR2 receptor, encoded by the TNFRSF1B polymorphic gene. We aimed to examine the effects of single nucleotide variants TNFRSF1B c.587T>G, c.*188A>G, c.*215C>T, and c.*922C>T on the clinicopathological characteristics and survival of cutaneous melanoma (CM) patients. Patients were genotyped using RT-PCR. TNFRSF1B levels were measured using qPCR. Luciferase reporter assay evaluated the interaction of miR-96 and miR-1271 with the 3'-UTR of TNFRSF1B. The c.587TT genotype was more common in patients younger than 54 years old than in older patients. Patients with c.*922CT or TT, c.587TG or GG + c.*922CT or TT genotypes, as well as those with the haplotype TATT, presented a higher risk of tumor progression and death due to the disease effects. Individuals with the c.*922TT genotype had a higher TNFRSF1B expression than those with the CC genotype. miR-1271 had less efficient binding with the 3'-UTR of the T allele when compared with the C allele of the SNV c.*922C>T. Our findings, for the first time, demonstrate that TNFRSF1B c.587T>G and c.*922C>T variants can serve as independent prognostic factors in CM patients.

Preliminary Findings on the Salivary Metabolome of Hookah and Cigarette Smokers.

The aim of the study was to evaluate the salivary metabolomic profile of patients who habitually smoke hookah and cigarettes. The groups consisted of 33 regular and exclusive hookah smokers, 26 regular and exclusive cigarette smokers, and 30 nonsmokers. Unstimulated whole saliva was collected for the measurement of salivary metabolites by gas chromatography coupled with tandem mass spectrometry (GC-MS/MS). The MetaboAnalyst software was used for statistical analysis and evaluation of biomarkers. 11 smoking salivary biomarkers were identified using the area under receiving-operator curver criterion and threshold of 0.9. Xylitol and octadecanol were higher in cigarette smokers compared to controls; arabitol and maltose were higher in controls compared to cigarette smokers; octadecanol and tyramine were higher in hookah smokers compared to controls; phenylalanine was higher in controls compared to hookah smokers; and fructose, isocitric acid, glucuronic acid, tryptamine, maltose, tyramine, and 3-hydroxyisolvaleric acid were higher in hookah smokers compared to cigarettes smokers. Conclusions: The evaluation of the salivary metabolome of hookah smokers, showing separation between the groups, especially between the control versus hookah groups and cigarette versus hookah groups, and it seems to demonstrate that the use of hookah tobacco is more damaging to health.

Association of Clinical Aspects and Genetic Variants with the Severity of Cisplatin-Induced Ototoxicity in Head and Neck Squamous Cell Carcinoma: A Prospective Cohort Study.

BACKGROUND: Cisplatin (CDDP) is a major ototoxic chemotherapy agent for head and neck squamous cell carcinoma (HNSCC) treatment. Clinicopathological features and genotypes encode different stages of CDDP metabolism, as their coexistence may influence the prevalence and severity of hearing loss. METHODS: HNSCC patients under CDDP chemoradiation were prospectively provided with baseline and post-treatment audiometry. Clinicopathological features and genetic variants encoding glutathione S-transferases (GSTT1, GSTM1, GSTP1), nucleotide excision repair (XPC, XPD, XPF, ERCC1), mismatch repair (MLH1, MSH2, MSH3, EXO1), and apoptosis (P53, CASP8, CASP9, CASP3, FAS, FASL)-related proteins were analyzed regarding ototoxicity. RESULTS: Eighty-nine patients were included, with a cumulative CDDP dose of 260 mg/m2. Moderate/severe ototoxicity occurred in 26 (29%) patients, particularly related to hearing loss at frequencies over 3000 Hertz. Race, body-mass index, and cumulative CDDP were independent risk factors. Patients with specific isolated and combined genotypes of GSTM1, GSTP1 c.313A>G, XPC c.2815A>C, XPD c.934G>A, EXO1 c.1762G>A, MSH3 c.3133A>G, FASL c.-844A>T, and P53 c.215G>C SNVs had up to 32.22 higher odds of presenting moderate/severe ototoxicity. CONCLUSIONS: Our data present, for the first time, the association of combined inherited nucleotide variants involved in CDDP efflux, DNA repair, and apoptosis with ototoxicity, which could be potential predictors in future clinical and genomic models.

Influence of IL1B (rs16944) and IL1R2 (rs4141134) polymorphisms on aggressiveness and prognosis of cutaneous melanoma.

Cutaneous melanoma is the most aggressive skin cancer with high mortality. Proinflammatory cytokines can modulate the proliferation and survival of cutaneous melanoma cells. Higher levels of interleukin-1ß (IL1B) were associated with tumor cell proliferation, invasion, and migration, and the IL-1 type II receptor (IL1R2) serves as an endogenous inhibitor of IL1B signaling. Single-nucleotide variations (SNVs) in these genes (IL1B rs16944 and IL1R2 rs4141134) can modulate cytokine production and binding; however, their role in cutaneous melanoma is still unknown. Thus, we investigated the influence of the above SNVs in clinicopathological aspects and cutaneous melanoma patients' survival. In the present study, we analyzed 193 patients with cutaneous melanoma for IL1B c.-598T>C (rs16944) and IL1R2 c.-2009G>A (rs4141134) genotypes with TaqMan assays. Differences between groups were calculated using χ2 or Fisher's exact test and multiple logistic regression. Progression-free survival (PFS) and melanoma-specific survival were calculated by Kaplan-Meier and Cox methods. The prognostic value of IL1R2 was also analyzed by the online consensus survival webserver for skin cutaneous melanoma (OSskcm). We found that IL1R2 rs4141134 GG genotype was more common in patients with nodular subtype (49.1% vs. 29.8%, P = 0.01) and the frequency of IL1R2 rs4141134 GG or GA was higher in patients with Clark levels III-V (87.4% vs. 75.8%, P = 0.04). Patients with IL1R2 rs4141134 GG or GA genotypes presented lower PFS (hazard ratio: 3.12, 95% confidence interval, 1.10-8.79, P = 0.03) when compared with AA genotype, supported by OSskcm results. Thus, our study presented for the first time preliminary evidence that IL1R2 rs4141134 SNV may modulate cutaneous melanoma clinicopathological aspects and survival possible by allowing IL1B signaling.

E-cig might cause cell damage of oral mucosa.

OBJECTIVE: The aim of this study was to investigate cytogenetic and cytotoxic damage through the evaluation of micronuclei (MN) and metanuclear anomalies in the oral mucosa of electronic cigarette (e-cig) users. STUDY DESIGN: The patients were recruited into 4 groups: e-cig users, smokers, former smokers, and nonsmokers (control). The samples were collected by means of exfoliative cytology of the lateral region of the tongue and the floor of the mouth. The smears obtained were fixed and stained by the Feulgen method for investigation of MN and metanuclear anomalies. RESULTS: A significant difference was observed for MN frequency only between the smoker and control groups. As for metanuclear anomalies, significant differences were observed: karyolysis between: smokers and control, e-cig and control, as well as former smokers; karyorrhexis: between smoker and control; binucleation: between e-cig and former smoker, as well as control; broken eggs: between e-cig and all other groups; nuclear bud: between e-cig and former smokers, as well as control. CONCLUSIONS: E-cig and alcohol users presented genotoxicity and cytotoxicity in the oral mucosa cells. The use of e-cigs and alcohol by former smokers can cause more damage to the cells of the oral mucosa compared to those who have not used e-cigs.

Influence of CASP9 c.-1339A>G and CASP3 c.-1191A>G variants in outcome of patients with head and neck squamous cell carcinoma.

BACKGROUND: Abnormalities in the intrinsic apoptosis pathway, associated with single nucleotide variants (SNVs) in caspase (CASP) genes, alter head and neck squamous cell carcinoma (HNSCC) proliferation and progression. This prospective study aimed to evaluate whether CASP9 c.-1339A>G and CASP3 c.-1191A>G SNVs influence the outcome of patients with HNSCC. Two hundred sixty-two HNSCC patients were enrolled in the study. METHODS: DNA and RNA of peripheral blood samples were analyzed using real-time polymerase chain reaction (PCR) for genotyping and quantitative PCR method for gene expression, respectively. Differences in CASP3 expressions were analyzed using the Mann-Whitney test. Event-free survival (EFS) and overall survival (OS) were calculated using the Kaplan-Meier curves, log-rank test, and Cox analyses. RESULTS: CASP3 c.-1191AG or GG genotype was associated with higher CASP3 expression when compared with AA genotype (0.50 arbitrary units (AUs) ± 0.29 standard deviation (SD) vs 0.28 AUs ± 0.12 SD; P = .02). Patients with CASP9 c.-1339GG genotype had 1.54 more chance of presenting disease progression or relapse than patients with CASP9 c.-1339AA or AG genotype. Patients with CASP9 c.-1339GG and CASP3 c.-1191GG combined genotype had 2.64 more chance of presenting progression or relapse of the disease and 2.84 more chance of evolving to death than those with the remaining combined genotypes. CONCLUSIONS: Our findings provide, for the first time, preliminary evidence that inherited abnormalities in the intrinsic apoptosis pathway, related to CASP9 c.-1339A>G and CASP3 c.-1191A>G SNVs, act as predictors of HNSCC patients' survival.

Superexpressão de genes da via Wnt/b-catenina no carcinoma de células escamosas bucal / Overexpression of Wnt/ß-catenin pathway genes in oral squamous cell carcinoma

O presente trabalho tem como proposição avaliar a expressão de genes da via de sinalização Wnt no carcinoma de células escamosas bucal (CCE). Foram avaliados dois grupos: Grupo controle (GCO): 12 amostras de mucosa bucal com aspecto de normalidade. Grupo carcinoma (GCA): 30 amostras com diagnóstico histopatológico de CCE. As informações quanto ao hábito tabágico, consumo de etílicos, gradação e estágio da doença foram extraídas dos prontuários. A expressão dos genes WNT5A, APC, CTNNB1, CCND1, MYC foi avaliada por meio de RT-qPCR e, os resultados de expressão gênica foram correlacionados com os dados clinicopatológicos dos pacientes. Os dados foram analisados por meio do software GraphPad Prism 5.03. Utilizou-se o teste t de Student e os coeficientes de correlação de Pearson e de Sperman, com nível de significância de 5% para todos os testes. Houve superexpressão dos genes, WNT5A (fold increase=0,28; p=0,034), APC (fold increase=0,74; p=0,043), CTNNB1 (fold increase=0,36; p=0,493), CCND1 (fold increase=0,67; p= 0,049) e MYC (fold increase=0,99; p=0,001) no GCA, quando comparado ao GCO. Ainda, a expressão do gene MYC apresentou correlação inversamente proporcional com o consumo de cigarros por dia (-3,76; p=0,040) e carga tabágica (-3,73; p=0,043). Já a expressão do gene CTNNB1 apresentou correlação inversamente proporcional ao Teste de Fagerström (-0,405; p=0,026) e a gradação histopatológica (-0,419; p=0,021). A via de sinalização Wnt/ßcatenina mostrou-se envolvida na carcinogênese bucal das amostras estudadas, por meio da superexpressão dos genes WNT5A, APC, CCND1 e MYC. Interessantemente, o aumento da expressão de CTNNB1 correlacionou-se com menor carga tabágica da mesma forma que o MYC com menor número de cigarros diários e menor carga tabágica. Assim, sugere-se que o papel da via Wnt parece ser importante nos estágios iniciais da carcinogênese bucal e que a ativação ou superexpressão dos genes se dá de maneira independente ao hábito tabágico(AU)

This study aim was to investigate the Wnt signaling genes expression in oral squamous cell carcinoma (SCC). Patients were divided into 2 groups: Control group (COG): 12 samples of oral mucosa with normal appearance. Carcinoma group (CAG): 30 samples of histopathological SCC diagnosis. Smoking habits, alcohol consumption, disease histopathological grade and clinical staging were accessed from medical records. The expression of the WNT5A, APC, CTNNB1, CCND1 and MYC genes was evaluated by RT-qPCR and the gene expression profile were correlated with the clinicopathological data of the patients. The groups were compared by the Student t-test, with p < 0.05 indicating a significant difference. The gene expression results were correlated with clinical data with Pearson's and Sperman's correlation coefficient. It was seen an overexpression of WNT5A (fold increase=0,28; p=0,034), APC (fold increase=0,74; p=0,043), CTNNB1 (fold increase=0,36; p=0,493), CCND1 (fold increase=0,67; p= 0,049) e MYC (fold increase=0,99; p=0,001) compared to COG. The Wnt / ß-catenin signaling pathway was shown to be involved in the oral carcinogenesis of the studied samples, through the overexpression of the WNT5A, APC, CCND1 and MYC genes. Interestingly, the increased expression of CTNNB1 was correlated to a lower load in the same way as MYC was correlated to a lower number of daily cigarettes and a lower smoking load. Thus, it is suggested that the role of the Wnt pathway appears to be important in the early stages of oral carcinogenesis and that the activation or overexpression of genes occurs independently of smoking(AU)

Forced international migration for refugee food: a scoping review / Migração internacional forçada e alimentação de refugiados: uma scoping review

Abstract Recent crisis and conflicts in African countries, the Middle East and the Americas have led to forced population migration and rekindled concern about food security. This article aims to map in the scientific literature the implications of forced migration on food and nutrition of refugees. Scoping Review, and database search: databases: PubMed Central, LILACS, SciElo, Science Direct and MEDLINE. Languages used in the survey were: English, Portuguese and Spanish, with publication year from 2013 to 2018. 173 articles were obtained and after removing of duplicates and full reading, 26 articles were selected and submitted to critical reading by two reviewers, resulting in 18 articles selected. From the analysis of the resulting articles, the following categories emerged: Food Inequity; Cultural Adaptation and Nutrition; Emerging Diseases and Strategies for the Promotion of Nutritional Health. Food insecurity is a marked consequence of forced international migration, and constitutes an emerging global public health problem, since concomitant with increasing population displacements also widens the range of chronic and nutritional diseases.

Resumo As recentes crises e conflitos em países Africanos, no Oriente Médio e Américas têm originado migração forçada de populações e reacende a preocupação com os cuidados com a alimentação. O objetivo deste artigo é mapear na literatura científica as implicações da migração forçada sobre a alimentação e nutrição de refugiados. Scoping Review, com buscas nas bases de dados: bases de dados: PubMed Central, LILACS, SciElo, Science Direct e MEDLINE. Os idiomas de pesquisa foram: Inglês, Português e Espanhol, e ano de publicação compreendido entre 2013 e 2018. Obteve-se 173 artigos e após remoção dos duplicados e leitura integral, 26 artigos foram selecionados e submetidos à leitura crítica por dois revisores independentes, resultando em 18 artigos selecionados. Da análise dos resultados dos artigos, emergiram as categorias: Iniquidade Alimentar; Adaptação Cultural e Nutrição; Doenças Emergentes e Estratégias de Promoção da Saúde Nutricional. A insegurança alimentar é consequência marcante da imigração internacional forçada, e se constitui um emergente problema de saúde pública global, pois concomitante aos crescentes deslocamentos populacionais também se ampliam a gama de doenças crônicas e nutricionais.

Forced international migration for refugee food: a scoping review.

Recent crisis and conflicts in African countries, the Middle East and the Americas have led to forced population migration and rekindled concern about food security. This article aims to map in the scientific literature the implications of forced migration on food and nutrition of refugees. Scoping Review, and database search: databases: PubMed Central, LILACS, SciElo, Science Direct and MEDLINE. Languages used in the survey were: English, Portuguese and Spanish, with publication year from 2013 to 2018. 173 articles were obtained and after removing of duplicates and full reading, 26 articles were selected and submitted to critical reading by two reviewers, resulting in 18 articles selected. From the analysis of the resulting articles, the following categories emerged: Food Inequity; Cultural Adaptation and Nutrition; Emerging Diseases and Strategies for the Promotion of Nutritional Health. Food insecurity is a marked consequence of forced international migration, and constitutes an emerging global public health problem, since concomitant with increasing population displacements also widens the range of chronic and nutritional diseases.

CASP8 (rs3834129) and CASP3 (rs4647601) polymorphisms in oropharynx cancer risk, tumor cell differentiation, and prognosis in a cohort of the Brazilian population.

The objective of this research was to assess the association of genetic polymorphisms related to intrinsic apoptosis pathway CASP8 rs3834129 and CASP3 rs4647601 with the risk, clinical and pathological aspects, and survival of oropharynx squamous cell carcinoma (OPSCC) patients that received cisplatin and radiotherapy. The genotypes were identified in 198 patients with OPSCC and 200 controls using polymerase chain reaction methods. Chi square or Fisher's exact test and logistic regression were applied for the detection of differences between groups. Patients' genotypes were statistically evaluated considering the event-free survival and overall analysis using Kaplan-Meier estimate and Cox regression. CASP3 rs4647601 GG genotype (44.4% vs. 30.0%, p = 0.03) and G allele (63.9% vs. 55.5%, p = 0.04) were more common in patients with OPSCC than in controls. Carriers of GG genotype and G allele were under 1.78-fold and 1.40-fold increased risk of OPSCC than others, respectively. The frequency of CASP8 rs3834129 DD genotype was higher in patients with OPSCC with poorly differentiated or undifferentiated tumors when compared to others (34.5% vs. 16.1%, p = 0.02). No influence of CASP8 and CASP3 polymorphisms on OPSCC patients' survival was seen in this study. Our results indicate that inherited genetic variants in the intrinsic apoptosis pathway related to CASP3 rs4647601 and CASP8 rs3834129 polymorphisms may be an important determinant of OPSCC risk and tumor cell differentiation.

Persistent dysgeusia post-halitosis treatment: How does it impact the patients' quality of life?

Background: The objective of this study was to evaluate the quality of life and the presence of anxiety and depression in patients with dysgeusia post halitosis treatment. Material and Methods: Sixty patients were divided into three groups: Dysgeusia group (DG); Halitosis group (HG) and Control group (CG). The following instruments were used: Medical results study Short form health research of 36 items (SF-36), State-state anxiety inventory (STAI) and Self-report questionnaire-20 (SRQ-20). Results: Of the 60 subjects studied, 85% were female and 15% were male. The evaluation of SF-36 indicated a statistically significant correlation between some domains for DG and showed low scores for Mental Health. In relation to HG, low scores were obtained for Bodily Pain, Vitality and Emotional Role. The CG showed low scores for Bodily Pain, General Health and Vitality. STAI was significant when DG was compared to HG and CG. The mean SRQ-20 score was higher in DG compared with the other groups. Conclusions: Persistent dysgeusia post-halitosis treatment impacts on QoL generically in the Mental health do-main, and specifically in trait and state anxiety. Symptoms of depression were also seen in this group of patients

No disponible

Is DNA ploidy related to smoking?

BACKGROUND: In the oral cavity, genomic instability is caused by long-term exposure to carcinogens. The aim of this study was to evaluate the relationship between smoking and DNA ploidy. METHODS: Cytological material was obtained from patients participating in the Outpatient Smoking Treatment Program of the Heart Institute (INCOR-HCFMUSP), and of the Discipline of Oral Medicine (ICT-UNESP). The inclusion criteria for all groups were the absence of a history of malignant tumors, absence of clinical signs of changes in the selected area, and alcohol consumption of less than 3 units per week. Group 1:30 smokers before smoking cessation treatment; Group 2:30 non-smokers; Group 3:30 ex-smokers abstinent for at least 1 year. Cytological smears were collected from the floor of the mouth and border of the tongue and stained by Feulgen. Aneuploidy was evaluated using the ACIS® III system. RESULTS: The Kruskal-Wallis test showed no statistically significant difference (P = .4383) between the groups studied. No association between tobacco consumption and aneuploidy was observed in group 1 (P = 1) or group 2 (P = .68; Fisher's exact test). CONCLUSION: Smoking was not associated with changes in DNA content or the incidence of aneuploidy in normal oral mucosa.

Mandible metastasis of small cell lung cancer mimicking a residual cyst.

Small cell lung carcinoma (SCLC) is an uncommon tumor characterized by an aggressive behavior with early metastasis, usually to the contralateral lung, liver, brain, and bones. There are only five cases of this particular tumor metastasizing to the oral cavity described in the English literature. We present the case of metastatic SCLC in the mandible with radiographic findings resembling a residual cyst. A 66-year-old man with previous diagnosis and treatment for a SCLC was referred to the Stomatology Department with a history of persistent pain in the mandible 1 year after the inferior right pre-molar tooth extraction. The radiographic exam showed a well-delimited radiolucent area on that extracted tooth's region resembling a residual cyst. Biopsy was performed yielding the diagnosis of metastatic SCLC. The patient was referred to the clinical oncologist for chemotherapy. Although uncommon, this tumor should be included in the differential diagnosis of jawbone lesions, particularly when the patient presents a previous diagnosis of SCLC.

Mandible metastasis of small cell lung cancer mimicking a residual cyst

Small cell lung carcinoma (SCLC) is an uncommon tumor characterized by an aggressive behavior with early metastasis, usually to the contralateral lung, liver, brain, and bones. There are only five cases of this particular tumor metastasizing to the oral cavity described in the English literature. We present the case of metastatic SCLC in the mandible with radiographic findings resembling a residual cyst. A 66-year-old man with previous diagnosis and treatment for a SCLC was referred to the Stomatology Department with a history of persistent pain in the mandible 1 year after the inferior right pre-molar tooth extraction. The radiographic exam showed a well-delimited radiolucent area on that extracted tooth's region resembling a residual cyst. Biopsy was performed yielding the diagnosis of metastatic SCLC. The patient was referred to the clinical oncologist for chemotherapy. Although uncommon, this tumor should be included in the differential diagnosis of jawbone lesions, particularly when the patient presents a previous diagnosis of SCLC.

Emotional assessment of patients with oral lichen planus.

BACKGROUND: Oral lichen planus is a chronic immune-mediated disease with an estimated prevalence of 0.5-2.5% in the general population. Patients with oral lichen planus are often emotionally unstable and anxious and may develop concomitant systemic disorders. The objective of this study was to evaluate emotional characteristics of patients with oral lichen planus. METHODS: Two groups were studied: the first group consisted of 48 patients with a diagnosis of oral lichen planus, and the second group consisted of controls without the disease matched for age and gender at a proportion of 1:1. The emotional state of the patients was evaluated using the State-Trait Anxiety Inventory, SF-36 generic quality of life questionnaire, and the Self Reporting Questionnaire-20. RESULTS AND CONCLUSIONS: The present investigation demonstrated the presence of anxiety and depression in patients with oral lichen planus and a negative impact of the disorder on the patient's quality of life as indicated by impairment of the physical aspect, vitality, mental health, and social aspect domains. This could indicate that associated psychological treatment may be important in the follow-up of these patients.