Bovine upper alimentary squamous cell carcinoma associated with bracken fern poisoning: Clinical-pathological aspects and etiopathogenesis of 100 cases.

Upper digestive tract (UDT) cancer is rare in cattle, however in Southern Brazil, the UDT squamous cell carcinomas (SCCs) are relatively common and have been associated with bracken fern consumption and the presence of papillomas. Although a theory of pathogenesis considers bovine papillomavirus type 4 (BPV-4) as a cofactor in the development of these SCCs, some aspects of the etiopathogenesis of this disease need to be more investigated. In fact, detection of BPV-4 in UDT papillomas is scarce in other regions of the world and has not been performed in Brazil. Therefore, this study had two aims: 1) to analyze the epidemiological, clinical and pathological aspects of 100 natural cases of SCCs in the UDT of cattle grazing on bracken fern (Pteridium arachnoideum) highly contaminated areas, investigating the associations between these parameters; and 2) to investigate the presence of papillomavirus DNA by polymerase chain reaction (PCR) in the UDT papillomas (n = 47) from 30 cattle that also had UDT SCCs. There were statistically significant associations between clinical signs and tumor localization in the UDT; between histological grade of differentiation and tumor localization; and a trend towards significant association between histological grade of differentiation and presence of metastases. The average age of cattle with oropharyngeal SCCs was 7.39 years, with statistically significant difference comparing to cattle with esophageal SCCs (8.6 years). No statistical association was observed among other clinical-pathological parameters (growth pattern and primary site of the tumor) analyzed. No BPV DNA was detected in papillomas by PCR. Therefore, these results suggest the possibility that papillomas of the UDT are not necessarily associated with BPV infection.

Human Papillomavirus (HPV) L1 Serum Antibodies and the Risk of Subsequent Oral HPV Acquisition in Men: The HIM Study.

The role of antibody-mediated immunity in preventing newly acquired oral human papillomavirus (HPV) is not well understood. Among 1618 men participating in the HPV Infection in Men (HIM) Study, we evaluated oral rinses for HPV DNA and baseline sera for HPV-6, -11, -16, and -18 L1 antibodies. Thirty percent of men (486) were seropositive for ≥1 HPV type, and 25 men developed incident oral HPV infection (HPV-6 was detected in 7, HPV-11 in 0, HPV-16 in 17, and HPV-18 in 1). Cox models revealed that men with circulating antibodies to HPV-6, -11, -16, or -18 were not less likely to acquire type-specific oral HPV than men without antibodies (hazard ratio for the risk of acquiring HPV-6, -11, -16, or -18, 1.63; 95% confidence interval, .56-4.76).

Chronic Stress Improves NO- and Ca2+ Flux-Dependent Vascular Function: A Pharmacological Study / Estresse Crônico Melhora a Função Vascular Dependente de NO e Fluxo De Ca2+: Um Estudo Farmacológico

Background: Stress is associated with cardiovascular diseases. Objective: This study aimed at assessing whether chronic stress induces vascular alterations, and whether these modulations are nitric oxide (NO) and Ca2+ dependent. Methods: Wistar rats, 30 days of age, were separated into 2 groups: control (C) and Stress (St). Chronic stress consisted of immobilization for 1 hour/day, 5 days/week, 15 weeks. Systolic blood pressure was assessed. Vascular studies on aortic rings were performed. Concentration-effect curves were built for noradrenaline, in the presence of L-NAME or prazosin, acetylcholine, sodium nitroprusside and KCl. In addition, Ca2+ flux was also evaluated. Results: Chronic stress induced hypertension, decreased the vascular response to KCl and to noradrenaline, and increased the vascular response to acetylcholine. L-NAME blunted the difference observed in noradrenaline curves. Furthermore, contractile response to Ca2+ was decreased in the aorta of stressed rats. Conclusion: Our data suggest that the vascular response to chronic stress is an adaptation to its deleterious effects, such as hypertension. In addition, this adaptation is NO- and Ca2+-dependent. These data help to clarify the contribution of stress to cardiovascular abnormalities. However, further studies are necessary to better elucidate the mechanisms involved in the cardiovascular dysfunction associated with stressors. (Arq Bras Cardiol. 2014; [online].ahead print, PP.0-0) .

Fundamento: Estresse está associado com complicações cardiovasculares. Objetivos: O objetivo do presente estudo foi avaliar se o estresse crônico induz alterações vasculares, e se essas alterações são dependentes de óxido nítrico (NO) e Ca2+. Métodos: Ratos machos Wistar com 30 dias de idade foram separados em 2 grupos: controle (C) e Estresse (St). Utilizou-se estresse crônico de imobilização por 1 hora/dia, 5 dias/semana, 15 semanas. Pressão arterial sistólica foi avaliada. A função vascular foi avaliada em anéis aórticos. Curvas de concentração-efeito foram realizadas para noradrenalina, na presença de L-NAME ou prazosina, cloreto de potássio (KCl), acetilcolina e nitroprussiato de sódio. Também foi efetuado um estudo para avaliação para fluxo de Ca2+. Resultados: Estresse crônico induziu hipertensão e resposta vascular diminuída para noradrenalina e KCl e aumentada para acetilcolina. A pré-incubação com L-NAME eliminou a diferença para noradrenalina. A resposta contrátil vascular para Ca2+ foi reduzida em animais estressados. Conclusão: Nossos dados sugerem que a resposta vascular ao estresse crônico seria uma adaptação aos efeitos deletérios do estresse, incluindo a hipertensão. Além disso, esses mecanismos adaptativos dependem de liberação de NO e fluxo de Ca2+. Esses resultados ajudam a esclarecer os mecanismos envolvidos nas alterações cardiovasculares associadas ao estresse. Entretanto, mais estudos são necessários para a melhor compreensão desses mecanismos. .

Joint and independent effects of alcohol drinking and tobacco smoking on oral cancer: a large case-control study.

Alcohol drinking and tobacco smoking are assumed to have significant independent and joint effects on oral cancer (OC) development. This assumption is based on consistent reports from observational studies, which, however, overestimated the independent effects of smoking and drinking, because they did not account for the interaction effect in multivariable analyses. This case-control study sought to investigate the independent and the joint effects of smoking and drinking on OC in a homogeneous sample of adults. Case patients (N = 1,144) were affected by invasive oral/oropharyngeal squamous cell carcinoma confirmed histologically, diagnosed between 1998 and 2008 in four hospitals of São Paulo (Brazil). Control patients (N = 1,661) were not affected by drinking-, smoking-associated diseases, cancers, upper aero-digestive tract diseases. Cumulative tobacco and alcohol consumptions were assessed anamnestically. Patients were categorized into never/ever users and never/level-1/level-2 users, according to the median consumption level in controls. The effects of smoking and drinking on OC adjusted for age, gender, schooling level were assessed using logistic regression analysis; Model-1 did not account for the smoking-drinking interaction; Model-2 accounted for this interaction and included the resultant interaction terms. The models were compared using the likelihood ratio test. According to Model-1, the adjusted odds ratios (ORs) for smoking, drinking, smoking-drinking were 3.50 (95% confidence interval -95CI, 2.76-4.44), 3.60 (95CI, 2.86-4.53), 12.60 (95CI, 7.89-20.13), respectively. According to Model-2 these figures were 1.41 (95CI, 1.02-1.96), 0.78 (95CI, 0.48-1.27), 8.16 (95CI, 2.09-31.78). Analogous results were obtained using three levels of exposure to smoking and drinking. Model-2 showed statistically significant better goodness-of-fit statistics than Model-1. Drinking was not independently associated with OC, while the independent effect of smoking was lower than expected, suggesting that observational studies should be revised adequately accounting for the smoking-drinking interaction. OC control policies should focus on addictive behaviours rather than on single lifestyle risk factors.

Mortality trends and prediction of HPV-related cancers in Brazil.

Estimation of the size of a cancer group, either through number of cases or extrapolation of past observed trends, is indispensable to the planning of effective assistance measures. The aim of this study was to analyze the mortality trends of human papillomavirus-related cancers in Brazil by sex, in the period 1996-2010, and make predictions until the year 2025. All deaths registered as being a result of cervical cancer (ICD-10 code: C53), as well as those caused by vulvar and vaginal (C51 and C52), anal (C21), penile (C60), and oropharyngeal (C02, C09, C10) cancers, were registered. Adjusted rate calculations for each year were used to study the trends through the regression program 'Joinpoint'. Predictions were made using the Nordpred program, utilizing the age-period-cohort model. When analyzing separately by location, it was observed that penile and anal cancers in men presented an increasing trend for the entire period with a statistically significant annual percentage change of 4% for anal cancer and 1.4% for penile cancer. Predictions indicate a reduction in the risk of death due to oropharyngeal cancer in men and cervical, vulvar, and vaginal cancers in women. It was observed that the increase in the number of deaths occurs mainly because of population changes (size and age structure). In terms of risk, an increase is predicted for anal and penile cancers in men and consequently an increase in mortality rates is observed for these types of cancers, unlike what is expected for human papillomavirus-related cancers in women.

Do tobacco and alcohol modify protective effects of diet on oral carcinogenesis?

Recent systematic reviews concluded that the frequent consumption of fruits and vegetables is inversely associated with the risk of oral cancer. We assessed this association, specifically comparing results obtained to nonsmokers and smokers, as well to nondrinkers and drinkers. We conducted a case-control study involving 296 patients with oral squamous cell carcinoma (cases) attended in 3 major hospitals of São Paulo, Brazil, paired with 296 controls, recruited from outpatient units of the same hospitals. Multivariate models assessed the effect of fruits and salads according to smoking and drinking. The intake of fruit was associated with the prevention of the disease in the specific assessment among light [odds ratio (OR) = 0.46; 95% confidence interval (CI) = 0.27-0.78) and heavy (OR = 0.30; 95% CI = 0.14-0.65) smokers. The same was observed for vegetables consumption. For nonsmokers, no fruit (OR = 50; 95% CI = 0.22-1.12) or vegetable (for tomato, OR = 0.53; 95% CI = 0.31-0.93) was associated with reduced risk of oral and oropharyngeal cancer. Similar results were found in the stratified analysis according to drinking status with OR = 0.51 (95% CI = 0.30-0.87) and 0.18 for fruits (95% CI = 0.07-0.45), respectively, for light and heavy drinkers. This observation suggests that the protective effect of fruit and salad intake may modulate the deleterious effects from tobacco and alcohol.

Promoter hypermethylation in primary squamous cell carcinoma of the oral cavity and oropharynx: a study of a Brazilian cohort.

Epigenetic silencing of cancer-related genes plays an important role in oral/oropharyngeal squamous cell carcinoma (OSCC). We evaluated promoter hypermethylation of 4 cancer-related genes in OSCCs of a Brazilian cohort and determined its relationship with exposure to alcohol, tobacco, HPV infection and clinicopathological parameters. CDKN2A (cyclin-dependent kinase inhibitor 2A or p16), SFN (stratifin or 14-3-3 σ), EDNRB (endothelin receptor B) and RUNX3 (runt-related transcript factor-3) had their methylation patterns evaluated by MSP analysis in OSCC tumors (n = 45). HPV detection was carried out by PCR/RFLP. Aberrant methylation was detected in 44/45 (97.8 %) OSCC; 24.4 % at CDKN2A, 77.8 % at EDNRB, 17.8 % at RUNX3 and 97.8 % at SFN gene. There was no significant association between methylation patterns and clinical parameters. HPV (subtype 16) was detected in 3 out of 45 patients (6 %). Our findings indicate that HPV infection is uncommon and methylation is frequent in Brazilian OSCCs, however, EDNRB and SFN gene methylation are not suitable OSCC biomarkers due to indistinct methylation in tumoral and normal samples. In contrast, CDKN2A and RUNX3 genes could be considered differentially methylated genes and potential tumor markers in OSCCs.

Dietary patterns and risk of oral cancer: a case-control study in São Paulo, Brazil.

OBJECTIVE: To analyze the association between dietary patterns and oral cancer. METHODS: The study, part of a Latin American multicenter hospital-based case-control study, was conducted in São Paulo, Southeastern Brazil, between November 1998 and March 2002 and included 366 incident cases of oral cancer and 469 controls, frequency-matched with cases by sex and age. Dietary data were collected using a food frequency questionnaire. The risk associated with the intake of food groups defined a posteriori, through factor analysis (called factors), was assessed. The first factor, labeled "prudent," was characterized by the intake of vegetables, fruit, cheese, and poultry. The second factor, "traditional," consisted of the intake of rice, pasta, pulses, and meat. The third factor, "snacks," was characterized as the intake of bread, butter, salami, cheese, cakes, and desserts. The fourth, "monotonous," was inversely associated with the intake of fruit, vegetables and most other food items. Factor scores for each component retained were calculated for cases and controls. After categorization of factor scores into tertiles according to the distribution of controls, odds ratios and 95% confidence intervals were calculated using unconditional multiple logistic regression. RESULTS: "Traditional" factor showed an inverse association with cancer (OR=0.51; 95% CI: 0.32; 0.81, p-value for trend 0.14), whereas "monotonous" was positively associated with the outcome (OR=1.78; 95% CI: 1.78; 2.85, p-value for trend <0.001). CONCLUSIONS: The study data suggest that the traditional Brazilian diet, consisting of rice and beans plus moderate amounts of meat, may confer protection against oral cancer, independently of any other risk factors such as alcohol intake and smoking.

[Occupational status and cancer of the oral cavity and oropharynx]. / Ocupação e câncer da cavidade oral e orofaringe.

To estimate the risk of occupation in oral and oropharyngeal cancer, a hospital-based case-control study was conducted in Greater Metropolitan São Paulo, Brazil. The study included 325 cases and 468 controls, frequency-matched with cases by sex and age, and interviewed from January 1999 to March 2002. Occupational risks were examined by industry and job titles and restricted to males (266 cases, 362 controls). Odds ratios (OR) were calculated by unconditional logistic regression, controlling for age, smoking, and alcohol. Males working in vehicle maintenance shops (26 cases, 12 controls) showed adjusted OR = 2.45 (95%CI: 1.14-5.27), increasing among those employed 10 or more years (OR = 7.90; 95%CI: 2.03-30.72). Occupation as vehicle repair worker (14 cases, 7 controls) showed OR = 2.10 (95%CI: 0.78-5.68), increasing among workers exposed 10 or more years (OR = 26.21; 95%CI: 2.34-294.06). Other industries and occupations revealed OR higher than 1.5, but not statistically significant. In conclusion, employment in vehicle maintenance shops and occupation as vehicle repair worker showed risk for oral cancer, independently of smoking and alcohol. More prolonged exposure increased the risk.

Micronucleus investigation of alcoholic patients with oral carcinomas

The micronucleus test (MN) is used as an indicator of genotoxic exposition, since it is associated with chromosome aberrations. An increased mutation rate in oral squamous cells, indicated by an increased MN frequency, is also related to the development of oral carcinomas. We evaluated the frequencies of MN and other metanucleated anomalies in the buccal squamous cells of 30 alcoholics with oral or oropharyngeal carcinomas, and compared them to a control group of abstinent health individuals. Microscopic examination was made of 2000 cells per individual from each of three distinct areas of the mouth: around the lesion (A), opposite to the lesion (B) and in the upper gingival-labial gutter (C); C was used as a control region because of low tumor frequency. There was a seven-fold increase in MN frequency in region B, a three-fold increase in region A and a two-fold, though nonsignificant, increase in C; indicating a gradient of frequencies towards carcinogenesis: C ® A ® B. Comparisons of frequencies of various types of metanucleated cells: binucleated, karyorrhexis (KR), karyolysis (KL) and broken egg (BE) in patients and controls showed, with few exceptions, highly significant differences. This gave us a better understanding of the dynamics of this squamous epithelium, supporting a more efficient biomonitor based on these various metanucleated anomalies: the repair index . Also, the apparently contradictory results from regression analysis revealed that the MN frequency decreased with age and alcohol consumption, probably because of slow cell proliferation, and consequently led to a loss of homeostasis due to aging. In addition, in the analysis of nonparametric variables only one CAGE question was significant, confirming the effect of alcohol. In conclusion, the MN test and the repair index could be used for monitoring clinical evolution, by means of intra- and inter-individual cellular comparisons, in subjects with healed or surgically removed tumors or leukoplastic lesions, after chemo- or radiotherapeutic treatments.

Micronucleus investigation of alcoholic patients with oral carcinomas.

The micronucleus test (MN) is used as an indicator of genotoxic exposition, since it is associated with chromosome aberrations. An increased mutation rate in oral squamous cells, indicated by an increased MN frequency, is also related to the development of oral carcinomas. We evaluated the frequencies of MN and other metanucleated anomalies in the buccal squamous cells of 30 alcoholics with oral or oropharyngeal carcinomas, and compared them to a control group of abstinent health individuals. Microscopic examination was made of 2000 cells per individual from each of three distinct areas of the mouth: around the lesion (A), opposite to the lesion (B) and in the upper gingival-labial gutter (C); C was used as a control region because of low tumor frequency. There was a seven-fold increase in MN frequency in region B, a three-fold increase in region A and a two-fold, though nonsignificant, increase in C; indicating a gradient of frequencies towards carcinogenesis: C --> A --> B. Comparisons of frequencies of various types of metanucleated cells: binucleated, karyorrhexis (KR), karyolysis (KL) and broken egg (BE) in patients and controls showed, with few exceptions, highly significant differences. This gave us a better understanding of the dynamics of this squamous epithelium, supporting a more efficient biomonitor based on these various metanucleated anomalies: the repair index RI=(KL+KR)/(MN+BE). Also, the apparently contradictory results from regression analysis revealed that the MN frequency decreased with age and alcohol consumption, probably because of slow cell proliferation, and consequently led to a loss of homeostasis due to aging. In addition, in the analysis of nonparametric variables only one CAGE question was significant, confirming the effect of alcohol. In conclusion, the MN test and the repair index could be used for monitoring clinical evolution, by means of intra- and inter-individual cellular comparisons, in subjects with healed or surgically removed tumors or leukoplastic lesions, after chemo- or radiotherapeutic treatments.

Risk factors for cancer of the oral cavity and oro-pharynx in Cuba.

In terms of worldwide levels, Cuba has an intermediate incidence of cancer of the oral cavity and oro-pharynx. We studied 200 cases of cancer of the oral cavity and pharynx, of whom 57 women (median age = 64) and 200 hospital controls, frequency matched with cases by age and sex, in relation to smoking and drinking history, intake of 25 foods or food groups, indicators of oral hygiene and sexual activity, and history of sexually transmitted diseases. Odds ratios (OR) and 95% confidence intervals (CI) were obtained from unconditional multiple logistic regressions and adjusted for age, sex, area of residence, education, and smoking and drinking habits. In the multivariate model, high educational level and white-collar occupation, but not white race, were associated with halving of oral cancer risk. Smoking > or =30 cigarettes per day showed an OR of 20.8 (95% CI: 8.9-48.3), similar to smoking > or =4 cigars daily (OR = 20.5). Drinking > or = 70 alcoholic drinks per week showed an OR of 5.7 (95% CI: 1.8-18.5). Hard liquors were by far the largest source of alcohol. Increased risk was associated with the highest tertile of intake for maize (OR = 1.9), meat (OR = 2.2) and ham and salami (OR = 2.0), whereas high fruit intake was associated with significantly decreased risk (OR = 0.4). Among indicators of dental care, number of missing teeth and poor general oral condition at oral inspection showed ORs of 2.7 and 2.6, respectively. Number of sexual partners, marriages or contacts with prostitutes, practice of oral sex and history of various sexually transmitted diseases, including genital warts, were not associated with oral cancer risk. 82% of oral cancer cases in Cuba were attributable to tobacco smoking, 19% to smoking cigars or pipe only. The fractions attributable to alcohol drinking (7%) and low fruit intake (11%) were more modest. Thus, decreases in cigarette and cigar smoking are at present the key to oral cancer prevention in Cuba.

Nontoxic, mutagenic, and clastogenic activities of Mate-Chimarrão (Ilex paraguariensis).

Aqueous extracts of Ilex paraguarariensis (mate-chimarrão), a species that belongs to the Aquifoliaceae family, were analyzed for the presence of genotoxic, mutagenic, and clastogenic activities through bacterial trials based on the induction of the SOS functions, as well as in human lymphocytes in vitro and in mammalian cells in vivo. The extracts of mate-chimarrão were genotoxic, as assessed by lysogenic induction in Escherichia coli, and they also induced mutagenesis in Salmonella typhimurium. They addition of S9 microsomal fraction, catalase, thiourea, or dipyridyl counteracted the genotoxic activity of mate-chimarrão, suggesting that oxygen reactive species play an essential role in the genotoxicity of mate-chimarrão extracts. The extracts were not clastogenic in vivo (bone marrow cells of rats) in our experimental conditions, but we have observed an increased frequency of chromosomal aberrations in mate-chimarrão-treated human peripheral lymphocytes. Our results suggest that a high consumption of mate-chimarrão can potentiate carcinogenesis in the human oropharynx and esophagus.

Controle do tabagismo: um desafio

Utiliza os dados apresentados pelos coordenadores de programas contra o fumo na 3ª Reuniäo Brasileira de Programas de Combate ao Fumo, realizada em Salvador no ano de 1989. Propöe estratégias e açöes a serem desenvolvidas pelos órgäos envolvidos em atividades anti-tabágicas. Os dados adicionais, coletados posteriormente pelos editores, complementam este perfil do controle do tabagismo no país

Black tobacco, wine and mate in oropharyngeal cancer. A case-control study from Uruguay.

A case-control study of oral and pharyngeal cancer involving interviews with 108 cases and 286 controls was carried out in the University Hospital of Montevideo, Uruguay. The study was restricted to males and cases afflicted with lip, salivary gland and nasopharyngeal cancer were excluded. Point estimates of RR associated with smoking variables, alcohol variables, nutritional items and ingestion of hot infusions of the herb Ilex paraguariensis ('Mate') were obtained by logistic regression analysis. Dark tobacco smokers showed a RR 3.4 times higher than light tobacco users and heavy drinkers of wine displayed an OR of 17.2. Mate exposure showed a significant dose-response, after adjustment for age, tobacco and alcohol intake, with a fivefold increase in risk for heavy consumers. Joint exposure to black tobacco and wine displayed very high risks and no significant interactions were observed. The results suggest that the high rates of oropharyngeal cancer could be explained by the multiplicative effect of black tobacco smoking, wine drinking and mate ingestion.

Black tobacco, wine and mate in oropharingeal cancer: a case control study from Uruguay

A case-control study of oral and pharyngeal cancer involving interviews with 108 cases and 286 controls was carried out in the University Hospital of Montevideo, Uruguay. The study was restricted to males and cases afflicted with lip, salivary gland and nasopharyngeal cancer were excluded. Point estimates of RR associated with smoking variables, alcohol variables, nutritional items and ingestion of hot infusions of the herb Ilex Paraguapensis (Mate) were obtained by logistic regression analysis. Dark tobacco smokers showed a RR 3.4 times higher than light tobacco users and heavy drinkers or wine displayed an OR of 17.2. Mate exposure showed a significant dose-response, after adjustement for age, tobacco and alcohol intake, with a fivefold increase in risk for heavy consumers. Joint exposure to black tobacco and wine displayed very high risks and no significant interactions were observed. The results suggest that the high rates of oropharyngeal cancer could be explained by the multiplicative effect of black tobacco smoking , wine drinking and mate ingestion (AU)